Establishment of a headspace-thermal desorption and gas chromatography-mass spectrometry method (HS-TD-GC-MS) for simultaneous detection of 51 volatile organic compounds in human urine: Application in occupational exposure assessment.

Volatile organic compounds (VOCs) are a group of ubiquitous environment pollutants especially released into the workplace. Assessment of VOCs exposure in occupational populations is therefore a crucial issue for occupational health. However, simultaneous biomonitoring of a variety of VOCs is less studied. In this study, a simple and sensitive method was developed for the simultaneous determination of 51 prototype VOCs in urine by headspace-thermal desorption coupled to gas chromatography-mass spectrometry (HS-TD-GC-MS). The urinary sample was pretreated with only adding 0.50 g of sodium chloride to 2 mL of urine and 51 VOCs should be determined with limits of detection (LODs) between 13.6 ng/L and 24.5 ng/L. The method linearity ranged from 0.005 to 10 µg/L with correlation coefficients (r) of 0.991 to 0.999. The precision for intraday and inter-day, measured by the variation coefficient (CV) at three levels of concentration, was below 15 %, except for 4-isopropyl toluene, dichloromethane, and trichloromethane at low concentration. For medium and high levels, recoveries of all target VOCs were within the standard range, but 1,1-dichloropropene and styrene, which were slightly under 80 % at low levels. In addition, the proposed method has been used to determine urine samples collected in three times (before, during and after working) from 152 workers at four different factories. 41 types of prototype VOCs were detected in workers urine. Significant differences (Kruskal-Wallis chi-squared = 117.18, df = 1, P < 0.05) in the concentration levels of VOCs between the exposed and unexposed groups were observed, but not between the three sampling times (Kruskal-Wallis chi-squared = 3.39, df = 2, P = 0.183). The present study provides an alternative method for biomonitoring and assessing mixed exposures to VOCs in occupational populations.

VDR regulates mitochondrial function as a protective mechanism against renal tubular cell injury in diabetic rats.

PURPOSE: To investigate the regulatory effect and mechanism of Vitamin D receptor (VDR) on mitochondrial function in renal tubular epithelial cell under diabetic status. METHODS: The diabetic rats induced by streptozotocin (STZ) and HK-2 cells under high glocose(HG)/transforming growth factor beta (TGF-ß) stimulation were used in this study. Calcitriol was administered for 24 weeks. Renal tubulointerstitial injury and some parameters of mitochondrial function including mitophagy, mitochondrial fission, mitochondrial ROS, mitochondrial membrane potential (MMP), mitochondrial ATP, Complex V activity and mitochondria-associated ER membranes (MAMs) integrity were examined. Additionally, paricalcitol, 3-MA (an autophagy inhibitor), VDR over-expression plasmid, VDR siRNA and Mfn2 siRNA were applied in vitro. RESULTS: The expression of VDR, Pink1, Parkin, Fundc1, LC3II, Atg5, Mfn2, Mfn1 in renal tubular cell of diabetic rats were decreased significantly. Calcitriol treatment reduced the levels of urinary albumin, serum creatinine and attenuated renal tubulointerstitial fibrosis in STZ induced diabetic rats. In addition, VDR agonist relieved mitophagy dysfunction, MAMs integrity, and inhibited mitochondrial fission, mitochondrial ROS. Co-immunoprecipitation analysis demonstrated that VDR interacted directly with Mfn2. Mitochondrial function including mitophagy, mitochondrial membrane potential (MMP), mitochondrial Ca2+, mitochondrial ATP and Complex V activity were decreased dramatically in HK-2 cells under HG/TGF-ß ambience. In vitro pretreatment of HK-2 cells with autophagy inhibitor 3-MA, VDR siRNA or Mfn2 siRNA negated the activating effects of paricalcitol on mitochondrial function. Pricalcitol and VDR over-expression plasmid activated Mfn2 and then partially restored the MAMs integrity. Additionally, VDR restored mitophagy was partially associated with MAMs integrity through Fundc1. CONCLUSION: Activated VDR could contribute to restore mitophagy through Mfn2-MAMs-Fundc1 pathway in renal tubular cell. VDR could recover mitochondrial ATP, complex V activity and MAMs integrity, inhibit mitochondrial fission and mitochondrial ROS. It indicating that VDR agonists ameliorate renal tubulointerstitial fibrosis in diabetic rats partially via regulation of mitochondrial function.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Mitofusin2 Ameliorated Endoplasmic Reticulum Stress and Mitochondrial Reactive Oxygen Species Through Maintaining Mitochondria-Associated Endoplasmic Reticulum Membrane Integrity in Cisplatin-Induced Acute Kidney Injury.

Aims: This study investigated the regulatory effect of Mitofusin2 (Mfn2) on mitochondria-associated endoplasmic reticulum membrane (MAM) integrity and cellular injury in cisplatin-induced acute kidney injury (CP-AKI). Results: CP-AKI mice exhibited decreased expression of Mfn2, increased expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), abnormal mitochondrial morphology, and reduced MAMs integrity, accompanied by the activation of mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress (inositol-requiring enzyme 1 [IRE1] and PERK pathways). In in vitro studies, CP-induced mitochondrial ROS, ER-stress activation, and increased apoptosis were accompanied by the downregulation of Mfn2 and MAMs integrity reduction in Boston University mouse proximal tubular cells (BUMPT) and human proximal tubular epithelial cells (HK-2). Pretreatment of BUMPT cells with the Mfn2 plasmid partially restored the integrity of MAMs, negatively controlled IRE1 and PERK pathways, and inhibited cell apoptosis. In contrast, ER-stress and MAMs integrity violations were increased after Mfn2 small-interfering RNA (siRNA) treatment in HK-2 cells under CP treatment. Coimmunoprecipitation analysis demonstrated that Mfn2 interacted with PERK and IRE1. Furthermore, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acadesine (AICAR), had a similar effect to Mfn2 plasmid in the regulation of ER stress and MAMs. Conversely, the ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), had no effect on the expression of Mfn2 and MAMs integrity. Innovation and Conclusion: This is the first study to explore the association between MAMs, ER stress, and Mfn2 in CP-AKI. Downregulation of Mfn2 expression abolished the MAMs integrity, and induced ER stress, mitochondrial ROS, and tubular cell apoptosis. This suggests that the Mfn2-MAMs pathway is a potential therapeutic target in CP-AKI. Antioxid. Redox Signal. 40, 16-39. The Ethical Registration number of animal experiment in this study was CSU-2022-01-0095.

Endogenous Zinc-Ion-Triggered In Situ Gelation Enables Zn Capture to Reprogram Benign Hyperplastic Prostate Microenvironment and Shrink Prostate.

Benign prostatic hyperplasia (BPH) as the leading cause of urination disorder is still a refractory disease, and there have no satisfied drugs or treatment protocols yet. With identifying excessive Zn2+ , inflammation, and oxidative stress as the etiology of aberrant hyperplasia, an injectable sodium alginate (SA) and glycyrrhizic acid (GA)-interconnected hydrogels (SAGA) featuring Zn2+ -triggered in situ gelation are developed to load lonidamine for reprogramming prostate microenvironment and treating BPH. Herein, SAGA hydrogels can crosslink with Zn2+ in BPH via coordination chelation and switch free Zn2+ to bound ones, consequently alleviating Zn2+ -arisen inflammation and glycolysis. Beyond capturing Zn2+ , GA with intrinsic immunoregulatory property can also alleviate local inflammation and scavenge reactive oxygen species (ROS). Intriguingly, Zn2+ chelation-bridged interconnection in SAGA enhances its mechanical property and regulates the degradation rate to enable continuous lonidamine release, favoring hyperplastic acini apoptosis and further inhibiting glycolysis. These multiple actions cooperatively reprogram BPH microenvironment to alleviate characteristic symptoms of BPH and shrink prostate. RNA sequencing reveals that chemotaxis, glycolysis, and tumor necrosis factor (TNF) inflammation-related pathways associated with M1-like phenotype polarization are discerned as the action rationales of such endogenous Zn2+ -triggered in situ hydrogels, providing a candidate avenue to treat BPH.

Myeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB.

The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation.

Compact multi-channel radio frequency pulse-sequence generator with fast-switching capability for cold-atom interferometers.

Cold-atom interferometers have matured into a powerful tool for fundamental physics research, and they are currently moving from realizations in the laboratory to applications in the field. A radio frequency (RF) generator is an indispensable component of these devices for controlling lasers and manipulating atoms. In this work, we developed a compact RF generator for fast switching and sweeping the frequencies and amplitudes of atomic-interference pulse sequences. In this generator, multi-channel RF signals are generated using a field-programmable gate array (FPGA) to control eight direct digital synthesizers (DDSs). We further propose and demonstrate a method for pre-loading the parameters of all the RF pulse sequences to the DDS registers before their execution, which eliminates the need for data transfer between the FPGA and DDSs to change RF signals. This sharply decreases the frequency-switching time when the pulse sequences are running. Performance characterization showed that the generated RF signals achieve a 100 ns frequency-switching time and a 40 dB harmonic-rejection ratio. The generated RF pulse sequences were applied to a cold-atom-interferometer gyroscope, and the contrast of atomic interference fringes was found to reach 38%. This compact multi-channel generator with fast frequency/amplitude switching and/or sweeping capability will be beneficial for applications in field-portable atom interferometers.

Exploration of diagnostic biomarkers, microenvironment characteristics, and ursolic acid's therapeutic effect for benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The study used Weighted Gene Co-Expression Network Analysis, as well as two machine learning strategies to identify BPH-specific biomarkers based on an integrated transcriptome data from 922 samples. Eight prognostic genes (ALCAM, COL6A2, CRISP2, FOXF2, IGF1, PTN, SCN7A, and UAP1) were identified to be BPH-specific biomarkers with high accuracy and specificity. Moreover, we constructed a seven-gene diagnostic classifier to distinguish BPH from PC. The infiltrations of plasmacytoid dendritic cells and neutrophil cells showed distinct differences between BPH and non-BPH groups. Additionally, ursolic acid can reverse transcriptional features associated with the occurrence and progression of BPH. Both in vivo and in vitro experiments have confirmed that it induces apoptosis of BPH cells and inhibits cell proliferation by promoting cell cycle S-phase arrest. The diagnostic biomarkers, microenvironment characteristics, and therapeutic effect of ursolic acid explored in this study offer new diagnostic and therapeutic strategies for BPH.

ELF3 promotes gemcitabine resistance through PKMYT1/CDK1 signaling pathway in gallbladder cancer.

BACKGROUND: Gemcitabine is the standard treatment for gallbladder cancer (GBC) patients, and the development of resistance frequently limits its efficacy. However, the molecular features and mechanisms of gemcitabine resistance (Gem-R) in GBC cells remain unknown. Herein, we aimed to explore the role of ELF3 in Gem-R of GBC, including the underlying mechanisms. METHODS: RNA sequencing was used to screen the essential genes related to the generation of Gem-R in GBC tissues. The correlation between Gem-R and ELF3 expression was identified in GDSC, GEO database, GBC tissues, and 3 GBC cell lines. Immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blot were used to examine the expression of ELF3, PKMYT1, and CDK1. Luciferase reporter assays were used to identify the binding site of ELF3 in the PKMYT1 promoter region. CCK-8 assay and clonogenic survival assays were used to evaluate the sensitivity of gemcitabine in GBC cells. A GBC xenograft model was used to evaluate the influence of ELF3 on the therapeutic effect of gemcitabine. RESULTS: A consistently positive correlation between ELF3 expression and Gem-R, both in newly generated GBC RNA-seq data and in the datasets from GDSC and GEO. Gem-R in GBC cells was facilitated by ELF3 overexpression, whereas ELF3 knockdown had the opposite effect. In vivo experiments further proved that reducing ELF3 expression promoted the gemcitabine sensitivity of GBC cells and extended the survival time of mice that received orthotopic xenografted tumors. Mechanistically, ELF3 upregulated PKMYT1 expression by interacting with the DNA binding region of PKMYT1 in GBC cells, thereby promoting the phosphorylation of CDK1 and inducing Gem-R. Treatment with a combination of the PKMYT1 shRNA and gemcitabine significantly reduced the growth of GBC cells induced by overexpression of ELF3 in vitro and in vivo. CONCLUSIONS: ELF3/PKMYT1/CDK1 axis significantly regulates Gem-R to GBC cells and may represent a promising drug target for treating GBC patients.

Exportin XPO7 acts as an oncogenic factor in prostate cancer via upregulation of TCF3.

PURPOSE: As a nuclear transport protein, XPO7 has been observed to show abnormal expression in various types of human cancers. However, the role of XPO7 in PCa remains elusive. METHODS: Here, in this study, immunohistochemistry and bioinformatics were used to determine the expression pattern and prognostic significance of XPO7. To investigate the functions of XPO7 in vitro and in vivo, we knocked down XPO7 in PCa cell lines and established xenograft mice models. Then, we used multiple experiments to determine the cell proliferation, migration, invasion, cell cycle and EMT in PCa cells after XPO7 modulation. Mechanistically, we conducted RNA-seq and identified the regulating effect of XPO7 on cell cycle-related and PI3K-AKT pathways. Furthermore, we assessed the regulating correlation between XPO7 and TCF3 and verified by a series of rescue experiments. RESULTS: We found a higher XPO7 expression in prostate cancer tissues and predicted a poorer prognosis of prostate cancer. Then, we further revealed that the ectopic expression of XPO7 in PCa cells facilitated cells proliferation, migration, cell cycle progression and EMT in vitro and promoted tumor growth in vivo. Mechanistically, we conducted RNA-seq and identified the regulating effect of XPO7 on cell cycle-related and PI3K-AKT pathways. Furthermore, a significantly positive correlation was discovered between the expression of XPO7 and TCF3. In addition, XPO7 may regulate PCa through mediating TCF3 expression. TCF3 depletion could alleviate the influence of XPO7 overexpression on malignant phenotypes of PCa cells. CONCLUSIONS: These findings indicate that XPO7 promotes PCa initiation and progression and that targeting XPO7 might be therapeutically beneficial to patients with PCa.

The antitumour effects of caloric restriction are mediated by the gut microbiome.

Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γ+CD8+ T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.

Molecular Mechanisms of Noncoding RNA in the Occurrence of Castration-Resistant Prostate Cancer.

Although several therapeutic options have been shown to improve survival of most patients with prostate cancer, progression to castration-refractory state continues to present challenges in clinics and scientific research. As a highly heterogeneous disease entity, the mechanisms of castration-resistant prostate cancer (CRPC) are complicated and arise from multiple factors. Among them, noncoding RNAs (ncRNAs), the untranslated part of the human transcriptome, are closely related to almost all biological regulation, including tumor metabolisms, epigenetic modifications and immune escape, which has encouraged scientists to investigate their role in CRPC. In clinical practice, ncRNAs, especially miRNAs and lncRNAs, may function as potential biomarkers for diagnosis and prognosis of CRPC. Therefore, understanding the molecular biology of CRPC will help boost a shift in the treatment of CRPC patients. In this review, we summarize the recent findings of miRNAs and lncRNAs, discuss their potential functional mechanisms and highlight their clinical application prospects in CRPC.

[Biological mechanisms of Oxalis corniculata regulating human prostate cancer PC-3 cells: An investigation based on the NF-κB pathway].

OBJECTIVE: To investigate the biological mechanisms underlying the effect of the Chinese herbal medicine Oxalis corniculata on human prostate cancer PC-3 cells. METHODS: Through in vitro experiment, we treated human prostate cancer PC-3 cells with different concentrations of Oxalis corniculata, assessed the viability of the cells by MTT assay, examined their apoptosis by flow cytometry, evaluated their migration and invasiveness by Transwell assay, and determined the expressions of the proteins p65, p-p65, IκBα and p-IκBα in the NF-κB pathway using protein imprinting technology. RESULTS: Compared with the blank control, Oxalis corniculata significantly inhibited the proliferation and induced the apoptosis of the PC-3 cells (P< 0.05), suppressed their migration and invasiveness in a dose-dependent manner (P< 0.05), and upregulated the expression of IκBα and downregulated those of p-p65 and p-IκBα in the NF-κB pathway (P< 0.05). CONCLUSION: Oxalis corniculata can inhibit the proliferation, migration and invasiveness and induce the apoptosis of human prostate cancer PC cells, which may be attributed to its abilities of inhibiting the expressions of p-p65 and p-IκBα and regulating the activity of the NF-κB pathway.

[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

[Mechanism of regulation of CNP rat model by oxalis decoction via cGAS-STING signaling pathway].

OBJECTIVE: To investigate the therapeutic mechanism of oxalis decoction on CNP rats by regulating cGAS-STING signaling pathway. METHODS: Thirty specific pathogen-free SD male rats were randomly divided into normal control group (NC), model control group (MC), and oxalis decoction group (OD),with 10 rats in each group.The left and right anterior abdominal lobes of each group were surgically exposed.The normal control group was injected by the same volume of normal saline.After the model was successfully established,the OD group was given ï¼»9.37g/(kg·d)ï¼½ by gavage once a day, and the NC and MC groups were given ï¼»0.01/(mｌ/g)ï¼½ normal saline by gavage. From the 7th day of administration, the body weight of the rats in each group was recorded every 7 days for dynamic comparison. After 50 days of administration, the prostate index of the rats in each group was calculated, the morphological and pathological changes of the prostate tissue were observed by HE staining,and the expression levels of tumor necrosis factorα(TNF-α), interleukin-1ß(IL-1ß)and IL-6 in serum were detected by ELISA. RT-qPCR was used to detect the mRNA expression of cGAS, STING, TRAF6 and HSP70 in prostate tissue of rats in each group. RESULTS: Versus the NC group and OD group, the prostate organ index in MC group was significantly higher than that in other groups (P<0.01). Versus the NC group, the HE staining results of the MC group showed that the prostate gland structure was disordered, and the interstitial and acinar epithelium were extensively edema, accompanied by a large number of lymphocyte infiltration, cell swelling, loose cytoplasm, and a small number of foam cells. Versus the MC group, HE staining showed that the edema of interstitial and acinar epithelial cells in the rat prostate tissue was reduced after the OD group intervention, and the inflammatory cell infiltration in the interstitium was significantly reduced.Versus to NC group, the expression levels of TNF-α,IL-1ßandIL-6 in MC group were significantly increased（P<0.01 ).Versus to MC group,the expression levels of TNF-α, IL-1ß and IL-6 in OD group were decreased (P<0.05). Versus the NC group, the mRNA expression of cGAS, STING and TRAF6 in the MC group was significantly up-regulated,and HSP70mRNA was significantly down-regulated(P<0.01).Versus the MC group,the OD group had significantly decreased mRNA expression of cGAS, STING and TRAF6 and significantly increased mrna expression of HSP70(P<0.05). CONCLUSIONS: CNP has autoimmune disorders that cause inflammatory responses.The key target for CNP treatment is to regulate innate immunity.The treatment with oxalis decoction can significantly improve the prostate organ index and pathological changes in CNP rats, which may be related to the down-regulation of cGAS-STING innate immune signaling pathway and the inhibition of inflammatory mediators secretion.

[Exploring the mechanism of levocarnitine in the treatment of epididymitis based on network pharmacology and molecular docking technology].

OBJECTIVE: To explore the potential mechanism of action of levocarnitine in the treatment of epididymitis based on network pharmacology and experimental research. METHODS: The target proteins related to epididymitis and levocarnitine were retrieved through multiple databases, and the common targets were obtained using Venny software. The protein-protein interactions were obtained using the STRING database. Cytoscape software was used for visualization, and key targets were selected after topological analysis. GO and KEGG pathway enrichment analysis was performed using the DAVID database. Molecular docking was performed using Autodock Vina. RESULTS: A total of 130 drug targets and 2 151 disease targets were obtained, with 47 common targets. Protein-protein interaction network analysis identified core targets of levocarnitine in the treatment of epididymitis, including AKT1, HSP90AA1, ALB, CASP3, GSK3B, and GSR. KEGG pathway analysis suggested that metabolic pathways, lipid metabolism and atherosclerosis, cancer pathways, fluid shear stress and atherosclerosis, measles, chemical carcinogens-reactive oxygen species, purine metabolism, PI3K-Akt, and other signaling pathways may be associated with the mechanism of levocarnitine in the treatment of epididymitis. CONCLUSION: This study revealed through network pharmacology that levocarnitine may act on multiple signaling pathways by targeting AKT1, HSP90AA1, ALB, CASP3, GSK3B, GSR, etc., thereby potentially exerting therapeutic effects on epididymitis.

Preemptive deep parasternal intercostal plane block for perioperative analgesia in coronary artery bypass grafting with sternotomy: a randomized, observer-blind, controlled study.

OBJECTIVE: The precise characteristics of deep parasternal intercostal plane block (DPIP), which is useful for providing analgesia during open heart surgery, have not yet been thoroughly elucidated. In this study, we aimed to establish the efficacy, define the cutaneous sensory block area, and determine the duration of preemptive DPIP block at the T3-4 or T4-5 intercostal spaces in patients undergoing coronary artery bypass grafting (CABG) via sternotomy. DESIGN: A prospective, single-blind, randomized controlled trial. SETTING: Patients were randomly divided into three cohorts, each containing thirty patients. PARTICIPANTS: Ninety patients who underwent elective CABG via sternotomy were included in this study. INTERVENTIONS: The T3-4 and T4-5 groups received a preoperative single-shot DPIP block at the respective intercostal spaces. The principal objective of the study was to ascertain the optimal dosage of sufentanil administered during surgical procedures involving either a DPIP block or its absence, and to conduct a comparative analysis thereof across distinct injection sites, specifically T3-4 and T4-5. Secondary factors considered were the dosage of postoperative analgesics, the extent of sensory block on the skin, pain levels after extubation, time of recovery from anesthesia (time to extubation), duration of the block, and the occurrence of nausea and vomiting. MEASUREMENTS & MAIN RESULTS: Preemptive DPIP block significantly reduced intraoperative sufentanil requirement compared to the control group (T3-4:0.38 ± 0.1, T4-5:0.32 ± 0.10, vs. Control:0.88 ± 0.3 µg/kg/h, p < 0.001). It also resulted in decreased analgesic consumption and numeric rating scale scores on the day of surgery (p < 0.01 compared to the control group). The DPIP block provided accurate anesthetic coverage of the dermatomes in the sternal region and reduced the time to extubation and postoperative nausea. However, the injection point (either via the T3-4 intercostal or the T4-5 intercostal) did not affect the efficacy. Preoperative DPIP block failed to provide adequate analgesia beyond 24 h post-surgery. CONCLUSION: Preemptive bilateral DPIP block provided effective analgesia in patients undergoing CABG during surgery and in the early postoperative period. The analgesic effects of the DPIP block in the T3-4 and T4-5 intercostal spaces were comparable.

Osteoglycin: An ECM Factor Regulating Fibrosis and Tumorigenesis.

The extracellular matrix (ECM) is made up of noncellular components that have special properties for influencing cell behavior and tissue structure. Small leucine-rich proteoglycans (SLRPs) are nonfibrillar ECM components that serve as structural scaffolds and signaling molecules. osteoglycin (OGN), a class III SLRP, is a ubiquitous ECM component that not only helps to organize the extracellular matrix but also regulates a number of important biological processes. As a glycosylated protein in the ECM, OGN was originally considered to be involved in fiber assembly and was reported to have a connection with fibrosis. In addition to these functions, OGN is found in a variety of cancer tissues and is implicated in cellular processes linked to tumorigenesis, including cell proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT). In this review, we summarize the structure and functions of OGN as well as its biological and clinical importance in the context of fibrotic illness and tumorigenesis. This review aims to improve our understanding of OGN and provide some new strategies for the treatment of fibrosis and cancer.

Nomogram to predict malignancy in branch duct type intraductal papillary mucinous neoplasms.

Prediction of malignancy in branch duct (BD)-type intraductal papillary mucinous neoplasms (BD-IPMNs) is difficult. In this retrospective study, we showed the performance of imaging biomarker and biochemical biomarker in identifying the malignant BD-IPMNs. A total of 97 patients with pathological proved BD-IPMNs were included in this study. Imaging data were collected from magnetic resonance imaging (MRI). Malignant BD-IPMNs were defined as those with high grade dysplasia and invasive carcinoma. There were 10 patients with malignant BD-IPMNs (10.3%). Significant difference was found in prevalence of mural nodule and tumor size >3.0 cm between patients with and without malignant BD-IPMNs (44.4% vs 3.1%, P < .01; 80.0% vs 33.3%, P < .01). Significant differences were observed in mural nodule and elevated carbohydrate antigen 19-9 (CA19-9) between patients with and without invasive carcinoma (40.0% vs 7.6, P = .05; 60% vs 15.3%, P = .04). Mural nodule and tumor size >3.0 cm were the independent associated factor for malignant BD-IPMNs. The odds ratio (OR) was 5.22 (95% confidence interval [CI]: 1.04-31.16) for mural nodule and was 6.80 (95% CI: 1.16-39.71) for cyst size >3.0 cm. The combined model of mural nodule and tumor size showed good performance in identifying malignant BD-IPMNs (area under the curve [AUC] = 0.82, 95%CI: 0.67-0.97). Our data show that mural nodule and cystic size can be used as predictor of malignancy in BD-IPMN. The predictive performance is acceptable.

MAFG-AS1 is a prognostic biomarker and facilitates prostate cancer progression.

Long Noncoding RNAs (LncRNAs) have recently been identified as key regulator in tumor progression. The LncRNA MAFG-AS1 has been reported to facilitate the progression of multiple cancers, however, its role in prostate cancer is still unknown. Here, we reported that MAFG-AS1 was upregulated in prostate cancer. Importantly, high expression of MAFG-AS1 indicated advanced stage prostate cancer. Univariate and Multivariate Cox regression analyses showed that high MAFG-AS1 expression was independently correlated with poor progression-free interval (PFI). According to the result of The Cancer Genome Atlas (TCGA) database and tissue microarray, high MAFG-AS1 expression indicated a poor prognosis in prostate cancer patients. In addition, gene functional enrichment analysis revealed that MAFG-AS1 may be involved in ribosome biogenesis, ribonucleoprotein complex subunit organization, ribonucleoprotein complex assembly, rRNA metabolic process, structural constituent of ribosome, and ribonucleoprotein complex binding. Furthermore, MAFG-AS1 knockdown by siRNA markedly impaired prostate cancer cell proliferation, migration, and invasion.