Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2-related Factor 2 Pathway.

ABSTRACT: Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD and normal aortic valves were collected. Sesn2 expression and sources were examined, and the results showed that Sesn2 expression was increased in aortic valves from patients with CAVD and was mainly secreted by macrophages. Additionally, U937 macrophages were pretreated with si-Sesn2 or cDNA-Sesn2 and further treated with oxidized low-density lipoprotein (ox-LDL); M1 macrophages and their markers were measured, and we found that pretreatment with si-Sesn2 increased ox-LDL-induced M1 macrophage polarization and marker mRNA levels, whereas pretreatment with cDNA-Sesn2 had the opposite effects. In ox-LDL-treated U937 macrophages, oxidative stress levels were increased in the si-Sesn2 pretreatment group and further increased by si-Nrf2 treatment, whereas oxidative stress levels were decreased in the cDNA-Sesn2 pretreatment group and significantly reversed by ML385, a specific Nrf2 inhibitor. The effects of Sesn2 on ox-LDL-induced oxidative stress and the osteogenic differentiation of ox-LDL-induced valvular interstitial cells (VICs) was examined by down-regulating Nrf2 pathway. When U937 macrophages were co-cultured with VICs, downregulation of Sesn2 increased ox-LDL-induced osteogenic differentiation in VICs, whereas overexpression of Sesn2 exerted the opposite effects. Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway.

The association between handgrip strength and depression in cancer survivors: a cross-sectional study.

BACKGROUND: The association between handgrip strength and depression in cancer survivors has been unexplored until now. We aim to examine the association between handgrip strength and depression in cancer survivors by using publicly available data (National Health and Nutrition Examination Survey). METHODS: Two waves of data from the National Health and Nutrition Examination Survey, from 2011-2012 and 2013-2014, were extracted and combined to explore this important issue. We extracted maximum patient handgrip strength value (from both hands). The Patient Health Questionnaire (PHQ-9) was used to evaluate depression with a cut-off > = 10 points indicating that patients had depressive symptoms. Other basic characteristics and health-related variables were also collected. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to select potential confounding factors. Multivariable linear or logistic regression models were adopted to explore whether handgrip strength as a continuous variable, or low handgrip strength, was associated with depressive symptoms. RESULTS: There were 876 cancer survivors in our present total sample, with 403 (46.0%) males and 473 females (54.0%). The mean (SD) age of the entire group was 64.67 (13.81) years. The prevalence of depression and low handgrip strength was 12.90% and 16.7%, respectively. The results showed that handgrip strength was negatively associated with depressive symptoms in cancer survivors (OR = 0.95, 95%CI:0.92-0.99; P = 0.024). In addition, after adjusting for age, gender, race; marital status, polypharmacy, sleep disorder, arthritis, congestive heart failure, history of stroke, type of cancer, chronic coronary bronchitis and being overweight, cancer survivors with low handgrip strength had a 2.02-fold risk of depression, compared to those with normal handgrip strength (OR = 2.02,95%CI:1.07-3.81; P = 0.028). CONCLUSIONS: Our present study suggests that low handgrip strength, as a simple and modifiable parameter, is associated with a higher risk of depression in cancer survivors. Therefore, future larger-scale prospective cohort studies are warranted to determine this association.

Enteromorpha prolifera Diet Drives Intestinal Microbiome Composition in Siganus oramin.

Enteromorpha prolifera (E. prolifera) contains complex sulfated polysaccharides that are resistant to biological degradation. Most organisms cannot digest biomass of E. prolifera, except Siganus oramin (S. oramin). This study was conducted to identify the bacteria in the intestine of S. oramin facilitating the digestion of E. prolifera polysaccharides (EPP). Metagenomic sequencing analysis of the S. oramin intestinal microbiota revealed that E. prolifera diet increased the number of Firmicutes, replacing Proteobacteria to be the dominant bacteria. The proportion of Firmicutes increased from 38.8 to 58.6%, with Bacteroidetes increasing nearly fivefold from 5 to 23.7%. 16S rDNA high-throughput sequencing showed that EPP-induced Bacteroidetes increased significantly in the intestinal flora of S. oramin cultivated in vitro. Metatranscriptome analysis showed that EPP induced more transferase, polysaccharide hydrolase, glycoside hydrolase, and esterases expressed in vitro, and most of them were taxonomically annotated to Bacteroidetes. Compared with the aggregation of GH family genes in metagenomic sequencing analysis in vivo, EPP induced more CBM32, GH2, GT2, GT30, and GH30 families gene expression in vitro. In general, We found that the bacteria in intestinal tract of S. oramin responsible for digestion of E. prolifera were Firmicutes and Bacteroidetes, while Bacteroidetes was the dominant bacteria involved in EPP degradation in vitro cultures. Compared with in vivo experiments, only GH family genes were mostly involved, we detected a more complete and complex EPP degradation pathway in vitro. The results may benefit the further study of biodegradation of E. prolifera and has potential implications for the utilization of E. prolifera for biotechnology.

Minimally invasive surgical approaches for spontaneous intracranial hemorrhage in neonates aged 0-3 months.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of minimally invasive surgical interventions in addressing spontaneous intracranial hemorrhage among neonates aged 0-3 months. METHODS: A retrospective analysis was conducted on a cohort of 30 neonates diagnosed with spontaneous intracranial hemorrhage, who underwent minimally invasive cranial trepanation and drainage procedures at our department between 2011 and 2015. RESULTS: A comprehensive follow-up, spanning a duration of 1-5 years, was conducted for all 30 neonates, revealing a 100% survival rate among the pediatric cohort. CONCLUSION: The findings suggest that minimally invasive cranial trepanation and drainage exhibit efficacy in neonates aged 0-3 months experiencing spontaneous intracranial hemorrhage, leading to a reduction in both mortality and disability rates. It is recommended that surgery be promptly performed upon definitive diagnosis and identification of operation indications to prevent severe brain damage resulting from prolonged intracranial hypertension and potential fatal outcomes in neonates. Furthermore, the surgical procedure is characterized by its simplicity, involving minimal trauma.

Bedside zero-fluoroscopy temporary permanent pacemaker implantation in the electrical storm treatment under the guidance of EnSite 3D system: a case report.

BACKGROUND: Electrical storm (ES) is a clinical emergency characterized by multiple malignant ventricular arrhythmias or ICD discharges within 24 h, requiring early rational management. CASE PRESENTATION: We report a 55-year-old man who underwent aortic valve replacement experienced recurrent ventricular tachycardia/ventricular fibrillation. A temporary permanent pacemaker with the EnSite system was implanted, and significant inhibition of the electrical storm, attributed to the atrial overdrive pacing, ensued. CONCLUSIONS: In emergency regarding an electrical storm, the bedside temporary permanent pacemaker implantation with the EnSite system is concluded to be feasible and safe.

Transdermal delivery of dextran using conductive microneedles assisted by iontophoresis.

The combination of microneedles (MNs) and iontophoresis (ITP) can enhance the drug penetration in the skin. We previously demonstrated the enhanced delivery of small molecule lidocaine in dentistry by the conductive MNs assisted by ITP. However, the delivery of macromolecules is yet to be explored for this strategy. This study fabricates conductive MNs with polyaniline and hyaluronic acid, which is combined with ITP to deliver dextran macromolecules. This combination improves the penetration of dextran molecules (3-5 kDa, 150 kDa, and 500 kDa) to a depth of around 1536 µm in the agarose gel model. Compared to non-conductive MNs assisted by ITP or conductive MNs alone, conductive MNs assisted by ITP also improves dextran's penetration through the skin, fat, muscle, and cartilage.

Study on the Efficacy of Electric Acupuncture in the Treatment of Premature Ejaculation Based on Testosterone Level.

Objective: To investigate the clinical efficacy and possible mechanism of electroacupuncture in the treatment of premature ejaculation. Methods: 50 cases of premature ejaculation patients who met the diagnostic criteria were randomly divided into 2 groups with 25 cases in each group. The observation group was treated with electroacupuncture, and the control group was treated with Longdan Xiegan decoction. The treatment period was 4 weeks. Ejaculation latency (IELT), sexual satisfaction score of patients, sexual satisfaction score of partners, testosterone test, and drug safety assessment were performed in all 4 groups before and after treatment. Results: IELT was prolonged in all groups after treatment, the difference was statistically significant (P < 0.05). At the same time, the IELT of the observation group was significantly higher than that of the control group after treatment. Life satisfaction scores of patients and spouses in 2 groups were improved after treatment compared with before treatment, the difference was statistically significant (P < 0.05). After treatment, the satisfaction scores of patients and spouses in the observation group were higher than those in the control group, and the difference was statistically significant (P < 0.05). Before treatment, there was no significant difference in serum testosterone levels among all groups (P > 0.05). Serum testosterone levels in all groups were decreased after treatment compared with before treatment, with statistical significance (P < 0.05). After treatment, the serum testosterone level of the observation group was lower than that of the control group, and the difference was statistically significant (P < 0.05). During the treatment, the adverse reactions in each group disappeared after treatment, and no obvious abnormality was observed in the safety indicators. Conclusion: Electroacupuncture can improve the symptoms of premature ejaculation, which may be related to the regulation of serum testosterone by acupuncture.

Treatment Strategies for Ventricular Septal Rupture After Myocardial Infarction: A Single-Center Experience.

Objective: To analyze treatment strategies, prognosis, and related risk factors of patients with postinfarction ventricular septal rupture, as well as the impact of timing of surgical intervention. Methods: A total of 23 patients diagnosed with postinfarction ventricular septal rupture who were non-selectively admitted to Shanxi Provincial Cardiovascular Hospital between October 2017 and August 2021 were included in this study. The relevant clinical data, operation-related conditions, and follow-up data were summarized for all patients. The Kaplan-Meier method and log-rank test were used for the cumulative incidence of unadjusted mortality in patients with different treatment methods. Multivariate logistic regression was used to evaluate the independent risk factors for in-hospital patient mortality. Results: The mean age of the study patients was 64.43 ± 7.54 years, 12(52.2%) were females. There was a significant difference in terms of postoperative residual shunt between the surgical and interventional closure groups (5.9 vs. 100%, respectively; P < 0.001). The overall in-hospital mortality rate was 21.7%; however, even though the surgical group had a lower mortality rate than the interventional closure group (17.6 vs. 33%, respectively), this difference was not statistically significant (P = 0.576). Univariate analysis showed that in-hospital survival group patients were significantly younger than in-hospital death group patients (62.50 ± 6.53 vs. 71.40 ± 7.37 years, respectively; P = 0.016), and that women had a significantly higher in-hospital mortality rate than men (P = 0.037). The average postoperative follow-up time was 18.11 ± 13.92 months; as of the end of the study all 14 patients in the surgical group were alive, Two out of four patients survived and two patients died after interventional closure. Univariate analysis showed that interventional closure was a risk factor for long-term death (P < 0.05). Conclusion: Surgical operation is the most effective treatment for patients with postinfarction ventricular septal rupture; however, the best timing of the operation should be based on the patient's condition and comprehensively determined through real-time evaluation and monitoring. We believe that delaying the operation time as much as possible when the patient's condition permits can reduce postoperative mortality. Interventional closure can be used as a supplementary or bridge treatment for surgical procedures.

BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation.

Lung cancer is one of the most prevalent and malignant cancers, among which lung adenocarcinoma (LUAD) accounts for the majority and remains a major cause of cancer-related mortality worldwide (Cui et al., 2019). Despite the growing intensity of research on the pathobiology and progression of lung cancer and the fact that many genes have been identified as potential drivers and targets for therapy (Luo et al., 2019; Zhang et al., 2019), the treatment and prognosis of lung cancer patients have hardly improved. Therefore, this study aimed to investigate the precise mechanism of lung cancer development and explore efficient diagnostic and therapeutic methods for clinical treatment.

Whole-transcriptome and proteome analyses identify key differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs associated with HCC.

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. To gain more insights into the transcriptomic landscape and molecular mechanism of HCC, we performed TMT-labelled tandem mass spectrometry (n = 4) and whole-transcriptome sequencing (n = 3) based on HCC tumour (T) and adjacent normal (N) tissues from seven HCC patients. To comprehensively evaluate the gene-regulatory circuits in HCC, differential expression and enrichment analyses were performed on the differentially expressed proteins (DEPs), genes (DEGs), miRNAs (555), lncRNAs (29) and circRNAs (895). A total of 977 proteins and 243 genes were found to be differentially expressed in HCC tumours compared with adjacent normal tissues. HCC data from The Cancer Genome Atlas were used to validate the results. Combined with the results above, 56 DEP-DEGs with common changes in relative quantity were identified. Functional pathway analysis showed that the DEP-DEGs were mainly enriched in the spliceosome and various metabolic processes. Bioinformatics analysis showed that hsa-miR-1266-5p, hsa-miR-128-1-5p, hsa-miR-139-5p, hsa-miR-34b-3p and hsa-miR-570-3p were involved in the regulation of the hub genes mentioned above. The crucial coexpression (lncRNA-mRNA, circRNA-mRNA) and competing endogenous RNA interaction axes showed the possible functions of the lncRNAs and circRNAs. We explored potential cancer biomarkers by combining proteomic and transcriptomic studies. Our study provides a valuable resource for understanding regulatory mechanisms at the RNA level and may ultimately further assist in the development of diagnostic and/or therapeutic targets for HCC.

Young age at diagnosis is associated with better prognosis in stage IV breast cancer.

Numerous studies have shown that young age is a risk factor in early breast cancer. But for stage IV breast cancer, it is unclear whether age has a similar effect on patient survival. We collected and analyzed data from patients with stage IV breast cancer between January 2010 and December 2015 in SEER database. Multivariate Cox proportional hazard model was used in this study. 13,069 patients with stage IV breast cancer were included in the analysis, of which 1,135 were young breast cancer patients (≤40 years old). In a multivariate analysis that adjusted for sociodemographic factors, clinical-pathological characteristics and therapeutic methods, the risk of death in patients with stage IV ≤40 years was significantly reduced (hazard ratio [HR], 0.72; 95% CI, 0.65-0.79). Subgroup analyses showed that, with the same adjustment of all factors, young age only significantly reduced the risk of death in patients with luminal A (HR, 0.78; 95% CI, 0.68-0.89) and luminal B (HR 0.46; 95% CI, 0.35-0.60) subtypes. Young age at diagnosis is associated with better survival in patients with stage IV breast cancer. The effect of young age at diagnosis on the survival outcome of stage IV breast cancer varies by subtypes.

[Analysis of Factors Influencing Prognosis of 87 Adults with Ph Chromosome Negative ALL].

OBJECTIVE: To explore the factors influencing total complete remission (CR), recurrence, disease-free survival (DFS) rate and overall survival (OS) rate in adults with Philadelphia (Ph) chromosome negative acute lymphoblastic leukemia (ALL) and the effect of subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) on prognosis. METHODS: The clinical data of 87 adult patients with Ph negative ALL were retrospectively analyzed, the CHOP regimen plus L-asparaginase (L-Asp) was used for the induction therapy, and the CHOP+ modified Hyper-CVAD or methotrexate was set up as the consolidation chemotherapy regimen. After consolidation chemotherapy for 3-6 courses, 45 patients (51.72%) received allo-HSCT , and 42 patients (48.28%) continually received the maintained consolidation chemotherapy. The average follow up time of the surviving patients was 40.13 (3-60 months). RESULTS: Out of 87 patients with Ph-ALL one patient died (1.15%). In 86 patients who could be evaluated, 68 cases (79.67%) reached CR at the end of 1 course, 80 cases obtained CR (93.02%). Multivariate regression analysis showed that the enlargement of lever, spleen and lymphomode, WBC count≥ 100×109/L were affecting factors for total CR (P<0.05). Among 80 cases with CR, 27 cases (33.75%) relapsed, 5 years' overall survival (OS) rate and disease-free survival (DFS) rate were 47.50% and 45.00% respectively. Multivariate regression analysis yet showed that the induction chemotherapy without L-Asp, presence of CNS leukemia at diagnosis, absence of allo-HSCT and no CR after indution chemotherapy for 4 weeks were affecting factors for relapse and poor prognosis of patients (P<0.05). According to 4 prognostic factors such as presence of CNS leukemia or no, WBC count≥100×109/L or no, induction chemotherapy with L-Asp or no and CR after induction chemotherapy for 4 weeks or no, 86 patients were divided into low-risk group (without poor prognostic factor), middle-risk group (with 1 poor prognostic factor), high-risk group (with 2-4 poor prognostic factors). Statistical results showed that allo-HSCT treatment in low-risk group had no significant effect on OS and DFS (P>0.05). The rate of OS and DFS in middle and high-risk group were significantly higher than those of patients without allo-HSCT treatment (P<0.05). CONCLUSION: Patients with central nervous system leukemia, high white blood cell count (≥100×109/L), induction chemotherapy without L-Asp, no CR after 4 weeks of chemotherapy and absence of allo-HSCT treatment are the factors influencing the prognosis of adult patients with Ph negative ALL, so the patients with those poor prognostic factors should take active treatment of allo-HSCT.

Gene cloning and characterization of an α-amylase from Alteromonas macleodii B7 for Enteromorpha polysaccharide degradation.

Enteromorpha polysaccharides (EP) extracted from green algae have displayed a wide variety of biological activities. However, their high molecular weight leads to a high viscosity and low solubility, and therefore, greatly restrains their application. To solve this problem, bacteria from the surface of Enteromorpha were screened, and an Alteromonas macleodii strain B7 was found to be able to decrease the molecular weight of EP in culture media. Proteins harvested from the supernatant of the A. macleodii B7 culture were subjected to native gel electrophoresis, and a band corresponding to the Enteromorpha polysaccharide lyase (EPL) was detected by activity staining. The enzyme identity was subsequently confirmed by MALDI-TOF/TOF mass spectrometry as the putative α-amylase reported in A. macleodii ATCC 27126. The amylase gene (amySTU) from A. macleodii B7 was cloned into Escherichia coli, resulting in highlevel expression of the recombinant enzyme with EP-degrading activity. AmySTU was found to be cold-adapted; however, its optimal enzyme activity was detected at 40°C. The α-amylase was highly stable over a broad pH range (5.5-10) with the optimal pH at 7.5-8.0. The highest enzyme activity was detected when NaCl concentration was 2%, which dropped by 50% when the NaCl concentration was increased to 16%, showing an excellent nature of halotolerance. Furthermore, the amylase activity was not significantly affected by tested surfactants or the presence of some organic solvents. Therefore, the A. macleodii strain B7 and its α-amylase can be useful in lowering EP molecular weight and in starch processing.

[Comparison of detection of trisomy 8 with fluorescence in situ hybridization and conventional karyotype analysis in myelodysplastic syndrome].

The purpose of this study was to compare the detection of trisomy 8 in myelodysplastic syndrome (MDS) patients with interphase fluorescence in situ hybridization (FISH) and cytogenetic karyotype analysis. Using Spectrum Green labeled chromosome 8 centromere probe, interphase FISH was established. The trisomy 8 clones were simultaneously detected in 48 MDS cases with FISH and conventional cytogenetic analysis (CCA). Results showed that the CCA revealed no significant difference of constitutional proportion between MDS-RA and MDS-RAEB with karyotypes of whole +8, partial +8 and one +8. With FISH, detectable rates were 66.1% for whole +8. Partial +8 and sole +8 were significantly higher than one +8 and complex +8, respectively. The percentages of trisomy 8 were similar in MDS-RA and MDS-RAEB. Trisomy 8 was detected in 1 of 15 specimens with normal or abnormal karyotype without trisomy 8 by FISH. There was linear correlation between the percentages of partial +8 detected by FISH and CCA. Two patients received CCA and FISH examination at diagnosis and during treatment, the percentage of trisomy 8 was increased with progress of disease. In conclusion, our results showed that FISH is a sensitive and accurate technique to detect trisomy 8 in MDS patients. It can provide contribute to diagnosis, assessment of curative effect and predicting progress of disease in MDS. Clone size of trisomy 8 does not related to classification of MDS, but sole +8 is seems to see in MDS-RA frequently.