Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the potential mechanism of Simiao Yongan decoction in the treatment of diabetic peripheral vascular disease based on network pharmacology and molecular docking technology

The study aims to investigate the potential action targets and molecular mechanisms of Simiao Yongan decoction (SMYAD) in treating diabetic peripheral vascular disease (DPVD) by utilizing network pharmacology analysis and molecular docking technology. The components and targets of SMYAD were screened using the TCMSP database, while DPVD-related genes were obtained from the GeneCards, OMIM, and Disgenet databases. After intersecting the gene sets, a Protein-Protein Interaction (PPI) network was established, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The practical chemical components and core targets identified were molecularly docked using AutoDock software. A total of 126 active compounds were screened from which 25 main components included quercetin, rutoside, hesperidin, naringin, and β-sitosterol were determined to be the active components most associated with the core targets. A total of 224 common target genes were obtained. Among them, JUN, AKT1, MAPK3, TP53, STAT3, RELA, MAPK1, FOS, and others are the expected core targets of traditional Chinese medicine. The top-ranked GO enrichment analysis results included 727 biological processes (BP), 153 molecular functions (MF), and 102 cellular components (CC). KEGG pathway enrichment analysis involved mainly 178 signaling pathways, such as cancer signaling pathway, AGE-RAGE signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, endocrine resistance signaling pathway, cell aging signaling pathway, and so on. The molecular docking results demonstrate that the principal chemical components of SMYAD exhibit considerable potential for binding to the core targets. SMYAD has the potential to treat DPVD through various components, targets, and pathways. Its mechanism of action requires further experimental investigation.
The mediation and interaction of the obesity index between moderate-vigorous recreational physical activity and hypertension

Previous studies showed that physical activity (PA) is concerned with hypertension (HTN). However, the mediation and interaction role of the obesity index: body mass index (BMI), waist-hip ratio (WHR), body fat rate (BFR) and visceral fat index (VFI) between PA and HTN has never been studied. Therefore, the purpose of this study was to assess the mediation and interaction of the obesity index between moderate-vigorous recreational physical activity (MVRPA) and HTN. We conducted a cross-sectional study of 4710 individuals aged 41 or older in Torch Development Zone, Zhongshan City. The mediation and interaction of the obesity index were evaluated by a four-way decomposition. 48.07% of participants had HTN among these groups. In the adjusted linear regression model, MVRPA was significantly correlated with WHR (β±SE = -0.005±0.002; P<0.05). Compared to sufficient MVRPA (odds ratio (OR) = 1.35), 95% (confidence interval (CI) = 1.17–1.56), insufficient MVRPA increased the risk of developing HTN. Furthermore, there were associations between BMI, WHR, BFR, VFI and HTN where the adjusted ORs and 95% CIs were 1.11 (1.09–1.13), 6.23 (2.61–14.90), 1.04 (1.03–1.06), 1.07 (1.06–1.09), respectively. The mediation analyses suggested that the impact of MVRPA on HTN risk may partly be explained by changes in obesity index, with a pure indirect mediation of WHR between MVRPA and HTN (P<0.05). Therefore, weight control, especially reducing abdominal obesity and maintaining adequate MVRPA, may lead to more proper control of HTN.
A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study

Background Filaggrin proteins are located in the skin and prevent epidermal water loss and impede the entry of micro-organisms, allergens and chemicals. Filaggrin null mutations are strongly associated with ichthyosis vulgaris and atopic dermatitis. Objective The authors aimed to investigate the association between filaggrin null mutations, atopic dermatitis and diabetes. Design A random sample of 3335 adults from the general population in Denmark was filaggrin-genotyped for R501X and 2282del4 null-mutations and questioned about atopic dermatitis and diabetes. Furthermore, two independent study populations of patients with type 1 (n=104) or 2 (n=774) diabetes were genotyped. Results In a crude data analysis, a positive association was detected between the filaggrin null genotype and, respectively, subjects from the general population who reported diabetes (p=0.04) and patients with established type 2 diabetes (p=0.073). Adjustment for age and gender resulted in significant associations for patients with type 2 diabetes (p=0.048) and subjects with self-reported diabetes (p=0.032). Conclusions Adult Danes with a filaggrin null genotype had a significantly increased prevalence of self-reported diabetes. This finding was replicated when an independent sample of Danish patients with established type 2 diabetes was compared with control subjects from the general population.
Impact of Bariatric Surgery on Left Ventricular Structure and Function

Background Obesity leads to an increased risk of cardiovascular disease morbidity and death, including heart failure. Bariatric surgery has been proven to be the most effective long‐term weight management treatment. This study investigated the changes in cardiac structure and function after bariatric surgery, including left ventricular global longitudinal strain. Methods and Results There were 398 consecutive patients who underwent bariatric surgery with pre‐ and postoperative transthoracic echocardiographic imaging at a US health system between 2004 and 2019. We compared cardiovascular risk factors and echocardiographic parameters between baseline and follow‐up at least 6 months postoperatively. Along with decreases in weight postoperatively, there were significant improvements in cardiovascular risk factors, including reduction in systolic blood pressure levels from 132 mm Hg (25th–75th percentile: 120–148 mm Hg) to 127 mm Hg (115–140 mm Hg; P=0.003), glycated hemoglobin levels from 6.5% (5.9%–7.6%) to 5.7% (5.4%–6.3%; P<0.001), and low‐density lipoprotein levels from 97 mg/dL (74–121 mg/dL) to 86 mg/dL (63–106 mg/dL; P<0.001). Left ventricular mass decreased from 205 g (165–261 g) to 190 g (151–236 g; P<0.001), left ventricular ejection fraction increased from 58% (55%–61%) to 60% (55%–64%; P<0.001), and left ventricular global longitudinal strain improved from −15.7% (−14.3% to −17.5%) to −18.6% (−16.0% to −20.3%; P<0.001) postoperatively. Conclusions This study has shown the long‐term impact of bariatric surgery on cardiac structure and function, with reductions in left ventricular mass and improvement in left ventricular global longitudinal strain. These findings support the cardiovascular benefits of bariatric surgery.
Pelvic drain placement after robot-assisted radical prostatectomy: meta-analysis

Abstract Background It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. Methods A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration’s risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). Results A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. −59.75 to 140.74 ml, P = 0.430, and mean difference −14.20 ml, 95% c.i. −32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien–Dindo grade I–II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien–Dindo grade III–V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference −0.08 days, 95% c.i. −0.45 to 0.29 days, P = 0.670, and mean difference −0.64 days, 95% c.i. −2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference −34.88 min, 95% c.i. −43.58 to –26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference −7.64 min, 95% c.i. −15.61 to 0.32 min, P = 0.060). Conclusion The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.
Horizontal ridge augmentation with porcine bone-derived grafting material: a long-term retrospective clinical study with more than 5 years of follow-up

Objectives The purpose of this study was to evaluate the outcomes of implants placed in horizontally augmented alveolar ridges using porcine bone grafts and to investigate the long-term stability of the porcine bone grafts. Materials and Methods A retrospective analysis was conducted on 49 sites that underwent horizontal ridge augmentation using porcine bone grafts and implant placement with a follow-up period longer than 5 years. Furthermore, additional analysis was conducted on 24 sites where porcine bone grafts were used exclusively for horizontal ridge augmentation and implant placement. Results The mean follow-up period after prosthesis loading was 67.5 months, with a mean marginal bone loss of 0.23 mm at 1 year and a cumulative mean marginal bone loss of 0.40 mm over the entire follow-up period. Of the 49 implants, 2 were lost and 3 did not meet the success criteria, resulting in a survival rate of 95.9% and a success rate of 89.8%. In 24 sites, the mean marginal bone loss was 0.23 mm at 1 year and 0.41 mm at 65.8 months, with 100% survival and success rates. Conclusion Porcine bone grafts can be successfully used in horizontal ridge augmentation for implant placement in cases of ridges with insufficient horizontal width.
Efficacy of cell-based immunotherapies on patients with glioma: an umbrella review of systematic reviews and meta-analysis protocol

Introduction Glial brain tumours are highly mortal and are noted as major neurosurgical challenges due to frequent recurrence or progression. Despite standard-of-care treatment for gliomas, the prognosis of patients with higher-grade glial tumours is still poor, and hence empowering antitumour immunity against glioma is a potential future oncological prospect. This review is designed to improve our understanding of the efficacy of cell-based immunotherapies for glioma. Methods and analysis This systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of main electronic databases: PubMed/MEDLINE, Scopus, ISI Web of Science EMBASE and ProQuest will be done on original articles, followed by a manual review of review articles. Only records in English and only clinical trials will be encountered for full-text review. All the appropriate studies that encountered the inclusion criteria will be screened, selected and then will undergo data extraction step by two independent authors. For meta-analyses, data heterogeneity for each parameter will be first evaluated by Cochran’s Q and I2 statistics. In case of possible heterogeneity, a random-effects meta-analysis will be performed and for homogenous data, fixed-effects models will be selected for reporting the results of the proportional meta-analysis. Bias risk will be assessed through Begg’s and Egger’s tests and will also be visualised by Funnel plots. Ethics and dissemination As this study will be a systematic review without human participants’ involvement, no ethical registration is required and meta-analysis will be presented at a peer-reviewed journal. PROSPERO registration number CRD42022373297
Early disengagement from HIV pre-exposure prophylaxis services and associated factors among female sex workers in Dar es Salaam, Tanzania: a socioecological approach

Introduction Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool when taken as prescribed. However, suboptimal use may challenge its real-life impact. To support female sex workers in their efforts to prevent themselves from HIV, it is essential to identify factors that contribute to early disengagement from PrEP care. In this study, we aimed to estimate the risk of early disengagement from PrEP services among female sex workers in Tanzania and associated factors using a socioecological model as a guiding framework. Methods The study was conducted as part of a pragmatic mHealth trial for PrEP roll-out in Dar es Salaam in 2021. We estimated the risk of early disengagement, defined as not presenting for the first follow-up visit (within 56 days of enrolment), and its associations with individual, social, behavioural and structural factors (age, self-perceived HIV risk, mental distress, harmful alcohol use, condom use, number of sex work clients, female sex worker stigma and mobility) using multivariable logistic regression models, with marginal standardisation to obtain adjusted relative risks (aRR). Results Of the 470 female sex workers enrolled in the study, 340 (74.6%) did not attend the first follow-up visit (disengaged). Mental distress (aRR=1.14; 95% CI 1.01 to 1.27) was associated with increased risk of disengagement. Participants who reported a higher number of clients per month (10–29 partners: aRR=0.87; 95% CI 0.76 to 0.98 and ≥30 partners: aRR=0.80; 95% CI 0.68 to 0.91) and older participants (≥35 years) (RR=0.75; 95% CI 0.56 to 0.95) had a lower risk of disengagement. Conclusions and recommendations Early disengagement with the PrEP programme was high. Mental distress, younger age and having fewer clients were risk factors for disengagement. We argue that PrEP programmes could benefit from including mental health screening and treatment, as well as directing attention to younger sex workers and those reporting fewer clients.
Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Abstract Background In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether a liquid biopsy that analyses blood derived exosomal hTERT transcript (e‐hTERT‐trans) may serve as such a biomarker in gliomas and meningiomas when compared to healthy controls. Methods Exosomes were isolated from the pre‐operative sera of patients' samples stored in the biobank of both Rabin and Sheba Medical Centers. The levels of e‐hTERT‐trans were measured in 81 healthy controls, 117 meningiomas, 17 low‐grade gliomas, and 61 glioblastomas. Clinical parameters of the patients were collected retrospectively and compared to the levels of the e‐hTERT‐trans. Results The upper normal limit of controls e‐hTERT‐trans was 1.85 relative quantitation (RQ). The rate of detection increased with rising tumor grade and correlated with tumor recurrence in meningiomas: mean RQ without recurrence (2.17 ± 11.7) versus with recurrence (3.59 ± 4.42; p = 0.002). In glioblastomas, preoperative measurements correlated with tumor volume and with the disease course on serial sampling. Conclusions We demonstrated for the first time that the expression of e‐hTERT‐trans transcript can be measured in the serum of primary brain tumors. This exosomal marker carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters. Future studies are required to investigate whether the sensitivity could be augmented and whether it can be implemented into routine patients care.
Obese Male Mice Exposed to Early Life Stress Display Sympathetic Activation and Hypertension Independent of Circulating Angiotensin II

Background We have previously reported that male mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show sympathetic activation and increased blood pressure in response to a chronic high‐fat diet. The goal of this study was to investigate the contribution of the renin–angiotensin–aldosterone system to the mechanism by which MSEW increases blood pressure and vasomotor sympathetic tone in obese male mice. Methods and Results Mice were exposed to MSEW during postnatal life. Undisturbed litters served as controls. At weaning, both control and MSEW offspring were placed on a low‐fat diet or a high‐fat diet for 20 weeks. Angiotensin peptides in serum were similar in control and MSEW mice regardless of the diet. However, a high‐fat diet induced a similar increase in angiotensinogen levels in serum, renal cortex, liver, and fat in both control and MSEW mice. No evidence of renin–angiotensin system activation was found in adipose tissue and renal cortex. After chronic treatment with enalapril (2.5 mg/kg per day, drinking water, 7 days), an angiotensin‐converting enzyme inhibitor that does not cross the blood–brain barrier, induced a similar reduction in blood pressure in both groups, while the vasomotor sympathetic tone remained increased in obese MSEW mice. In addition, acute boluses of angiotensin II (1, 10, 50 μg/kg s.c.) exerted a similar pressor response in MSEW and control mice before and after enalapril treatment. Conclusions Overall, elevated blood pressure and vasomotor sympathetic tone remained exacerbated in MSEW mice compared with controls after the peripheral inhibition of angiotensin‐converting enzyme, suggesting a mechanism independent of angiotensin II.
Mitofusin-2 Regulates Platelet Mitochondria and Function

BACKGROUND: Single-nucleotide polymorphisms linked with the rs1474868 T allele (MFN2 [mitofusin-2] T/T) in the human mitochondrial fusion protein MFN2 gene are associated with reduced platelet MFN2 RNA expression and platelet counts. This study investigates the impact of MFN2 on megakaryocyte and platelet biology. METHODS: Mice with megakaryocyte/platelet deletion of Mfn2 (Mfn2−/− [Mfn2 conditional knockout]) were generated using Pf4-Cre crossed with floxed Mfn2 mice. Human megakaryocytes were generated from cord blood and platelets isolated from healthy subjects genotyped for rs1474868. Ex vivo approaches assessed mitochondrial morphology, function, and platelet activation responses. In vivo measurements included endogenous/transfused platelet life span, tail bleed time, transient middle cerebral artery occlusion, and pulmonary vascular permeability/hemorrhage following lipopolysaccharide-induced acute lung injury. RESULTS: Mitochondria was more fragmented in megakaryocytes derived from Mfn2−/− mice and from human cord blood with MFN2 T/T genotype compared with control megakaryocytes. Human resting platelets of MFN2 T/T genotype had reduced MFN2 protein, diminished mitochondrial membrane potential, and an increased rate of phosphatidylserine exposure during ex vivo culture. Platelet counts and platelet life span were reduced in Mfn2−/− mice accompanied by an increased rate of phosphatidylserine exposure in resting platelets, especially aged platelets, during ex vivo culture. Mfn2−/− also decreased platelet mitochondrial membrane potential (basal) and activated mitochondrial oxygen consumption rate, reactive oxygen species generation, calcium flux, platelet-neutrophil aggregate formation, and phosphatidylserine exposure following dual agonist activation. Ultimately, Mfn2−/− mice showed prolonged tail bleed times, decreased ischemic stroke infarct size after cerebral ischemia-reperfusion, and exacerbated pulmonary inflammatory hemorrhage following lipopolysaccharide-induced acute lung injury. Analysis of MFN2 SNPs in the iSPAAR study (Identification of SNPs Predisposing to Altered ALI Risk) identified a significant association between MFN2 and 28-day mortality in patients with acute respiratory distress syndrome. CONCLUSIONS: Mfn2 preserves mitochondrial phenotypes in megakaryocytes and platelets and influences platelet life span, function, and outcomes of stroke and lung injury.
ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial–mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial–mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.