Ferrostatin-1 Inhibits Toll-Like Receptor 4/NF-κB Signaling to Alleviate Intervertebral Disc Degeneration in Rats.

Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, is implicated in intervertebral disc degeneration (IDD). The current study explored the role of Fer-1 in IDD via the toll-like receptor 4 (TLR4)/NF-κB signaling pathway. IDD-related gene expression microarray GSE124272 and high-throughput sequencing data set GSE175710 were obtained through the Gene Expression Omnibus database. Differentially expressed genes in IDD were identified, followed by implementation of protein-protein interaction network analysis and receiver operating characteristic curve analysis. The main pathways in IDD were obtained through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses, and target genes of Fer-1 were obtained through PubChem and PharmMapper websites. Finally, GPX4, FTH, and TLR4 expression was determined in a IDD rat model. Three key co-expression modules involved in IDD were obtained through Weighted Gene Co-Expression Network Analysis. Thirteen differentially expressed genes were found to be associated with IDD, and eight key genes (TLR4, BCL2A1, CXCL1, IL1R1, NAMPT, SOCS3, XCL1, and IRAK3) were found to affect IDD. These eight key genes had the diagnostic potential for IDD. The NF-κB signaling pathway was shown to play a predominant role in IDD development. Network pharmacologic analysis indicated a role of Fer-1 in suppressing ferroptosis and ameliorating IDD via the TLR4/NF-κB signaling pathway, which was verified by an in vivo animal experiment. The study showed that Fer-1 down-regulates TLR4 to inactivate NF-κB signaling pathway, suppressing ferroptosis and ultimately alleviating IDD in rats.

Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome.

BACKGROUND: Bisphenol A (BPA) levels are high in women with polycystic ovary syndrome (PCOS). The mechanism by which BPA induces abnormal glucose metabolism in PCOS patients is largely unknown. METHODS: Serum and urine samples were collected from women with and without PCOS (control) at the reproductive medicine center with informed consent. Non-PCOS patients who received in vitro fertilization were recruited for collection of ovarian follicular fluid and granular cells. Wild-type C57BL/6 and AhR -/- mice were used to verify the effects of BPA on PCOS. Real-time PCR, western blotting, and ELISA were conducted to analyze the function of BPA. Chip-qPCR verified the role of AhR in GLUT4 transcription. Flow cytometry was performed to determine glucose uptake. RESULTS: A positive correlation was observed between BPA concentration and serum BPA levels in PCOS patients. BPA aggravated the changes in PCOS with abnormal glucose metabolism, impaired fertility, and increased body fat. Mechanistically, we showed that BPA activated AhR and led to decreased glucose transport via GLUT4 downregulation in ovarian granular cells. Therefore, the use of inhibitors or knockout of AhR could effectively rescue BPA-induced metabolic disorders in PCOS mice. CONCLUSIONS: Our results revealed that BPA suppressed GLUT4 expression and induced abnormal glucose metabolism by activating AhR, causing insulin resistance, and is thus a potential contributor to the development of PCOS. Therefore, AhR could be a potential new therapeutic target for PCOS. Video Abstract.

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Clinicopathological, immunohistochemical and therapeutic approaches on survival in patients with epithelioid glioblastoma: Institutional experience in the management of 58 patients.

Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM.

Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity.

BACKGROUND: Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. METHODS: Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. RESULTS: A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. CONCLUSION: Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.

Oncologic and functional outcomes of different reconstruction modalities after resection of chondrosarcoma of the scapula: a medium- to long-term follow-up study.

OBJECTIVES: To evaluate the oncologic and functional results of scapular reconstruction after partial or total scapulectomy for chondrosarcoma. MATERIALS AND METHODS: Twenty-one patients with chondrosarcoma who underwent partial or total scapulectomy between January 2005 and July 2019 were reviewed retrospectively. RESULTS: At a mean follow-up of 62.6 months (range, 13-123 months), four patients developed local recurrence, and three developed distant metastases, one of which developed both recurrence and metastasis. The overall survival rate of patients at 5 years was 84.6%, the disease-free survival rate was 69.3%, and the complication rate was 19% (4/21). The 1993 American Musculoskeletal Tumor Society (MSTS93) scores of patients in the partial scapulectomy group, total scapulectomy + humeral suspension group and prosthetic reconstruction group were 26.50 ± 1.38, 19.00 ± 2.58, and 21.38 ± 2.62, respectively. There was a statistically significant difference between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group ( P = 0.006 and 0.0336, respectively). The range of motion of the shoulder joint for forward flexion was 80.83° ± 11.14°, 51.25° ± 21.36°, and 52.50° ± 11.02°, respectively. The p-values for the comparison between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group were 0.0493 and 0.0174, respectively. And the range of motion of abduction was 75.00° ± 10.49°, 32.50° ± 11.90°, 41.88° ± 11.63°, respectively. Patients in the partial scapulectomy group had significantly better postoperative shoulder abduction function than the total scapulectomy + humeral suspension or prosthetic reconstruction group (P = 0.0035 and 0.0304, respectively). There was no significant difference in MSTS93 scores and flexion and abduction function of the shoulder joint in the upper extremity after total scapulectomy with humeral suspension or prosthetic reconstruction (P > 0.05). CONCLUSIONS: Surgical treatment of chondrosarcoma of the scapula can achieve a satisfactory prognosis and shoulder function. Total scapulectomy followed by prosthetic reconstruction or humeral suspension are both feasible treatments.

Long-term results of trans-scaphoid perilunate fracture dislocations treated by open reduction and internal fixation.

PURPOSE: The paper holds the research purpose of confirming the long-term results of trans-scaphoid perilunate fracture dislocations (TSPFD) under the treatment of open reduction and internal fixation. METHODS: Anteroposterial-lateral radiographs of the patient's wrist were taken before and after surgery. We use a dorsal approach for all cases. Postoperative clinical and radiographic assessments were performed routinely. The scapholunate angle (SLA), estradiol angle (RLA), as well as lunotriquetral distance (LTD) assisted in the radiographic assessment. Clinical assessment was performed using the Krimmer score, modified Mayo wrist score (MWS), active flexion extension arc (FEA), radial deviation and ulnar deviation arc (RUDA) and grip strength. A visual analog scale (VAS) assisted in the pain evaluation, the VAS score ranges from 0 to 10. RESULTS: Twenty-two TSPFD patients due to the wrist trauma received operative treatment and we retrospectively analyzed the surgical results, together with evaluating their clinical and radiological follow-up. These patients held a mean age of 30 years old. Herzberg's perilunate fracture-dislocation classification was taken into account to find that 19 males and 3 females suffered dorsal dislocation. The fellow-up time lasted 98.3 months on average. All cases obtained sufficient union after open reduction and internal fixation. The last follow-up found the median of grip strength was 20.00 (interquartile range, 20.00-21.25), which was 84.5% of the normal side. The modified Mayo wrist score evaluation scale considered 12 cases as excellent, and 10 good. The median of VAS and Krimmer scores at the final follow-up were 1.50 (interquartile range, 0.75-2.00) and 100.00 (interquartile range, 100.00-100.00), respectively, higher relative to the pre-operation (P < 0.001). No patients showed nerve damage preoperatively or postoperatively, or pin tract infection in any of the patient. CONCLUSIONS: It is necessary to diagnose such complicated biomechanical damage in early stage and adopt the open reduction and stable fixation for treatment; appropriate treatment can contribute to a functionally adequate and anatomically integrated wrist.

A pilot prospective study of plasma cell-free DNA whole-genome sequencing identified chromosome 7p copy number gains as a specific biomarker for early lung cancer detection.

Chromosome 7 plays an important role in lung tumorigenesis. Chromosome 7 copy number changes might be an early event of lung cancer tumorigenesis. Here we investigate whether chromosome 7p copy number gain is a detectable genetic event with plasma cell-free DNA for early lung cancer detection. Eighteen surgical eligible lung cancer patients and eighteen non-cancer controls were recruited. Peripheral blood was collected before surgery. Cell-free DNA was profiled with low coverage whole-genome sequencing. Chromosome 7 copy number gains were defined as chr7 normalized coverage ≥1.0005 and p-value <0.05. Plasma cell-free DNA chr7 copy gains were then compared to pathological examinations on surgical tissues. 83.3% of patients were confirmed as malignancy post-operation, 12 patients with adenocarcinoma, and 3 with squamous-carcinoma. The other 16.7% were benign lesions. Cell-free DNA was successfully extracted from pre-surgical plasma samples, with a concentration range from 0.18 to 0.49 ng/µl. Chromosome 7 short arm copy gains were found in 66.7% (10/15) patients, including 66.7% (4/6) T1aN0M0 and 50.0% (1/2) Tis patients, otherwise, chr7p gain was found in 0% (0/3) benign lesions. The specificity was further examined in 18 volunteers who undergoing routine body examinations. Meanwhile, positive carcinoembryonic antigen (CEA) and cytokeratin-19-fragment (CYFRA21-1) were only found in 1/18 (5.7%) and 4/18 (22.2%), respectively. Taking together, Ultrasensitive- Chromosomal Aneuploidy Detector (UCAD) chr7p or UCAD chr7p and tumor biomarker positivity can predict 12/15 (80%, 95% CI: 49.0-94.3%) early lung cancers. Further analyses showed that chr7p copy number gains tend to be enriched in normal EGFR/KRAS patients (Fisher's test, p-value = 0.077). Chromosome 7p copy gain is a useful peripheral blood tumor biomarker from lung cancer detection.

SIRT1-ZEB1-positive feedback promotes epithelial-mesenchymal transition process and metastasis of osteosarcoma.

Osteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+ -dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in the development of malignant tumors. The study aimed to investigate the role of SIRT1 in osteosarcoma and explore its underlying oncogenic mechanisms. The prognostic value of SIRT1 in osteosarcoma was assessed through detection of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma cells were treated with small interfering RNA SIRT1 and overexpressed SIRT1 to detect the cell migration, invasion, and epithelial-mesenchymal transition (EMT). The levels of SIRT1 expression were significantly higher in osteosarcoma tissues than those in adjacent normal tissues, and the SIRT1 protein level may be coupled with metastatic and poor prognosis risk in patients with osteosarcoma. Moreover, SIRT1 silencing inhibited the migration as well as invasion ability of osteosarcoma cells in vitro, and SIRT1 upregulation reversed those effects. Finally, we found that SIRT1-ZEB1-positive feedback enhanced the EMT process and metastasis of osteosarcoma. Altogether, the results of the current study revealed that high levels of SIRT1 might be a biomarker for a high metastatic rate in patients with osteosarcoma, which suggested that inhibition of SIRT1 might be promising for the therapeutics of osteosarcoma.

Yak and Tibetan sheep trampling inhibit reproductive and photosynthetic traits of Medicago ruthenica var. inschanica.

Livestock grazing affects grassland stability, resilience, and productivity owing to trampling, foraging, and excretion. Over time, trampling influences a wide range of grassland components and can have lasting effects. Trampling helps maintain grassland health but may also cause its degradation. In a field experiment over two growing seasons, we simulated yak and sheep trampling at different intensities and investigated their effects on the reproductive and photosynthetic characteristics of Medicago ruthenica var. inschanica in a Tianzhu alpine meadow in Gansu Province, China. Our results show that simulated trampling inhibited the asexual and sexual reproduction and growth of M. ruthenica. The root surface area, root volume, root biomass, pod length, pod number per unit area, number of seeds per pod, thousand-seed weight, and seed yield were significantly reduced under simulated trampling in the upper 30 cm of soil (P < 0.05) but were not reduced in the deeper soil layers (> 30 cm). Light trampling by both yak and Tibetan sheep promoted photosynthesis, while heavy trampling by both species inhibited photosynthesis. Yak trampling inhibited photosynthesis more than Tibetan sheep trampling, and overall, the adverse effects of yak trampling on asexual and sexual reproduction and growth of M. ruthenica were greater than those of Tibetan sheep trampling. Thus, the effect of yak trampling is greater than the effect of trampling by Tibetan sheep, where the different trampling intensities of yak and Tibetan sheep can result in direct but varied influences on grasslands, potentially leading to grassland differentiation.

Predictable weathering of puparial hydrocarbons of necrophagous flies for determining the postmortem interval: a field experiment using Chrysomya rufifacies.

Preadult development of necrophagous flies is commonly recognized as an accurate method for estimating the minimum postmortem interval (PMImin). However, once the PMImin exceeds the duration of preadult development, the method is less accurate. Recently, fly puparial hydrocarbons were found to significantly change with weathering time in the field, indicating their potential use for PMImin estimates. However, additional studies are required to demonstrate how the weathering varies among species. In this study, the puparia of Chrysomya rufifacies were placed in the field to experience natural weathering to characterize hydrocarbon composition change over time. We found that weathering of the puparial hydrocarbons was regular and highly predictable in the field. For most of the hydrocarbons, the abundance decreased significantly and could be modeled using a modified exponent function. In addition, the weathering rate was significantly correlated with the hydrocarbon classes. The weathering rate of 2-methyl alkanes was significantly lower than that of alkenes and internal methyl alkanes, and alkenes were higher than the other two classes. For mono-methyl alkanes, the rate was significantly and positively associated with carbon chain length and branch position. These results indicate that puparial hydrocarbon weathering is highly predictable and can be used for estimating long-term PMImin.

[Effects of recombinant fusion protein interleukin-18 on expression of immune-inflammatory factors in mice infected with Staphylococcus aureus].

OBJECTIVE: To observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo. METHODS: A total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2ß mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR. RESULTS: Compared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2ß mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ. CONCLUSIONS: In the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.

Snapshot depth sensitive Raman spectroscopy in layered tissues.

Depth sensitive Raman spectroscopy has been shown effective in the detection of depth dependent Raman spectra in layered tissues. However, the current techniques for depth sensitive Raman measurements based on fiber-optic probes suffer from poor depth resolution and significant variation in probe-sample contact. In contrast, those lens based techniques either require the change in objective-sample distance or suffer from slow spectral acquisition. We report a snapshot depth-sensitive Raman technique based on an axicon lens and a ring-to-line fiber assembly to simultaneously acquire Raman signals emitted from five different depths in the non-contact manner without moving any component. A numerical tool was developed to simulate ray tracing and optimize the snapshot depth sensitive setup to achieve the tradeoff between signal collection efficiency and depth resolution for Raman measurements in the skin. Moreover, the snapshot system was demonstrated to be able to acquire depth sensitive Raman spectra from not only transparent and turbid skin phantoms but also from ex vivo pork tissues and in vivo human thumbnails when the excitation laser power was limited to the maximum permissible exposure for human skin. The results suggest the great potential of snapshot depth sensitive Raman spectroscopy in the characterization of the skin and other layered tissues in the clinical setting or other similar applications such as quality monitoring of tablets and capsules in pharmaceutical industry requiring the rapid measurement of depth dependent Raman spectra.

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/miR-138-5p/SLC7A11 Coexpression Regulation.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

[Timing and efficacy of surgical intervention for severe acute pancreatitis].

OBJECTIVE: To explore the indications, timing and approaches of surgical interventions for severe acute pancreatitis (SAP). METHODS: A retrospective study was performed for 115 hospitalized SAP patients from 2007 to 2013. RESULTS: Among them, 62 underwent surgery and another 53 were treated conservatively. The curative and mortality rates of surgical intervention and non-operation groups were 87.1%vs 84.9% (P > 0.05) and 9.68% vs 9.43% (P > 0.05) respectively. Twenty-five patients received early surgical intervention (<2 week) and another 37 delayed surgical intervention. The interval from diagnosis to surgical intervention of two groups were 7.5 ± 3.3 and 23.9 ± 8.5 days respectively. The mortality rates of early and delayed surgical groups were 16.0% and 5.4% respectively (P > 0.05). CONCLUSIONS: Individualized comprehensive therapy should be offered in the treatment of SAP. Timing of surgery for those with pancreatic necrosis and infection should be delayed to 3-4 weeks later until their general conditions permit.

[Types and risk factors of arrhythmia on young patients with acute coronary syndrome in Henan province].

OBJECTIVE: The types and risk factors of arrhythmia were analyzed on acute coronary syndrome (ACS) patients under the age of 44 years who were hospitalized in Henan province between September 2009 to June 2012. METHODS: Medical records of eligible patients were obtained from the information system of the First Affiliated Hospital of Zhengzhou University teleconsultation information center. Middle aged and elderly ACS patients who were hospitalized at the same period served as controls. Data on arrhythmia types, blood pressure, thyroid disease, respiratory sleep apnea syndrome, smoking history, history of alcohol consumption, eating habits, family history of early-onset arrhythmia, laboratory tests were analyzed. RESULTS: (1) Arrhythmia was detected in 110 out of young ACS patients (55%), which was significantly lower than that in the elderly ACS patients (71.05%, P < 0.01). (2) The top three arrhythmias in young ACS patients were: sinus tachycardia (30.50%), the premature ventricular contractions (19.00%), atrial flutter/atrial fibrillation (16.50%). Incidence of sinus tachycardia, atrial flutter/atrial fibrillation were significantly higher while incidence of ventricular tachycardia, ventricular fibrillation, paroxysmal supraventricular tachycardia were significantly lower in young ACS patients than in middle-aged ACS patients (all P < 0.05). The incidence of sinus tachycardia was higher while incidence of ventricular premature accelerated ventricular spontaneous cardiac rhythm, ventricular tachycardia, ventricular fibrillation, non-paroxysmal supraventricular tachycardia, atrial flutter/atrial fibrillation, paroxysmal supraventricular tachycardia, sinus bradycardia, nodal escape, atrioventricular block were significantly lower in young ACS patients than in elderly ACS patients (all P < 0.05). (3) Body mass index, incidence of smoking, coronary three-vessel disease, drinking, eating salty foods, thyroid dysfunction, sleep apnea were significantly higher in youth ACS patients with arrhythmia than in young ACS patients without arrhythmia (all P < 0. 05). (4) Logistic regression analysis found that number of diseased coronary vessels (OR = 24.293), smoking (OR = 1.112) and alcohol consumption (OR = 1.039) were independent risk factor for developing arrhythmia in young ACS patients from Henan province. CONCLUSIONS: The main types of arrhythmia are sinus tachycardia, premature ventricular contractions, atrial flutter/atrial fibrillation and the major risk factors related to the arrhythmia are number of diseased coronary vessels, smoking and alcohol consumption in young ACS patients from Henan province.

[Population characteristics and impact on heart rate variability, heart rate and blood pressure of passive smoking].

OBJECTIVE: To investigate the basic characteristics of passive smoking population, and the impact of passive smoking on heart rate variability, heart rate and blood pressure. METHODS: Eighty-six passive smokers [mean age: (52.4 ± 7.6) years] were recruited from patients and their relatives who visited cardiovascular outpatient department and excluded structural heart disease between June 2010 and June 2012, 80 normal subjects who were not exposed to smoking served as controls. Questionnaire survey, 24 hours ambulatory electrocardiogram examination and blood pressure measurement were performed in all recruited subjects. RESULTS: (1) Non-marriage rate [18.60% (16/86) vs. 3.75% (3/80), P < 0.01] was significantly higher while education level were significantly lower in passive smoking group than in control group. Passive smokers were more likely service industry workers [29.07% (25/86) vs. 15.00% (12/80), P < 0.05] and had longer daily working time [(7.56 ± 1.24) h vs. (6.02 ± 0.96) h, P < 0.01], and were less likely to be professional technology industry employers [20.93% (18/86) vs. 36.25% (29/80), P < 0.05] and managers [13.95% (12/86) vs. 38.75% (31/80), P < 0.01] compared to controls. The main place of passive smoking was workplace (67.44%, 58/86), entertainment venues (63.95%,55/86), restaurants (48.84%, 42/86). (2) Standard of the normal sinus RR intervals (SDNN), the normal consecutive sinus RR interval difference between the root-mean-square (rMSSD) and adjacent the difference between the RR interval>50 ms the number of share the percentage (PNN50) were significantly lower in passive smoking group than in the control group (all P < 0.05). Every 5 min average of the standard deviation of sinus RR cycle (SDNN index) and 24 h every 5 min sinus RR interval mean standard deviation (SDANN) were similar between the 2 groups (all P > 0.05). Ultra-low-frequency power (VLF), low frequency power (LF), high frequency power (HF) and LF/HF were significantly lower in passive smoking group than in the control group (all P < 0.01). (3) Heart rate and diastolic blood pressure were significantly higher in passive smoking group than in control group (all P < 0.05) while systolic blood pressure was similar between the 2 groups (P > 0.05). CONCLUSIONS: Marriage status, education level, profession and daily working time are independent determinants for passive smoking. Passive smoking mainly occurred in the workplace, entertainment venues and restaurants. Passive smoking is linked with reduced heart rate variability, increased 24 h average heart rate and diastolic blood pressure.

[Effect of the smoking cessation services in the out-patient department for patients with coronary heart disease].

OBJECTIVE: To evaluate the effects and clinical prognosis of out-patient department-based smoking cessation services for coronary heart disease (CHD) patients. METHODS: A total of 140 smoking patients diagnosed with coronary heart disease in our cardiovascular department were randomly divided into the intensive smoking cessation clinic follow-up group (intervention group, patients were informed on the importance and methods to quit smoking at the first visit and reminded for that at months interval for 6 months, n = 70) and the conventional treatment group (control group, n = 70). After 6 months, the smoking status, cardiovascular event rates, drug usage, out-patient medical costs and quality of life were compared between the two groups. RESULTS: Age, gender, concomitant diseases, drug usage were similar between the two groups at baseline (all P > 0.05). After 6 months, smoking quit rate [34.2% (24/70) vs. 5.7% (4/70), P < 0.01], drug use rates: lipid-lowering drugs [95.3% (67/70) vs. 80.4% (56/70)], ß blockers [82.4% (57/70) vs. 41.3% (28/70)], and ACEI/ARB [61.4% (43/70) vs. 34.4% (24/70)] were significantly higher in the intervention group than in the control group, while total cardiovascular event rates [21.4% (15/70) vs. 47.1% (33/70), P < 0.01] and out-patient medical costs (3789.3 RMB vs. 4984.2 RMB, P < 0.01) were significantly lower in the intervention group than in the control group. The quality of life scores derived from MYO health survey questionnaire was significantly higher in the intervention group than in the control group (P < 0.01). The top three reasons responsible for continuous smoking for all patients failed to quit smoking were: (1) others smoked more than me and still alive and healthy [90.3% (56/62)]; (2) smoking helped me to keep relaxed and reduce trouble in daily work and life [70.9% (44/62)]; (3) smoking was essential while chatting and drinking with friends [66.1% (41/62)]. The overall satisfactory rate to this smoking cessation program was 42.8% and the satisfactory rate was up to 50.0% by patients. CONCLUSIONS: Intensive outpatient smoking cessation follow-up program can significantly improve the smoking cessation rates, the guideline drug use rate and the quality of life while reduce medical costs for coronary heart disease patients.

[Relation between expression of cerebral beta-APP in the chronic alcoholism rats and death caused by TSAH].

OBJECTIVE: By observing the cerebral beta-amyloid precursor protein (beta-APP) expression in the chronic alcoholism rats with slight cerebral injury, to discuss the correlation of chronic alcoholism and death caused by traumatic subarachnoid haemorrhage (TSAH). METHODS: Sixty male SD rats were randomly divided into watering group, watering group with strike, alcoholism group and alcoholism group with strike. Among them, the alcohol was used for continuous 4 weeks in alcoholism groups and the concussion was made in groups with strike. In each group, HE staining and immunohistochemical staining of the cerebral tissues were done and the results were analyzed by the histopathologic image system. RESULTS: In watering group, there was no abnormal. In watering group with strike, mild neuronic congestion was found. In alcoholism group, vascular texture on cerebral surface was found. And the neurons arranged in disorder with dilated intercellular space. In alcoholism group with strike, diffuse congestion on cerebral surface was found. And there was TSAH with thick-layer patches around brainstem following irregular axonotmesis. The quantity of beta-APP IOD in alcoholism group was significantly higher in the frontal lobe, hippocampus, cerebellum, brainstem than those in watering group with strike and alcoholism group with strike. CONCLUSION: The cerebral tissues with chronic alcoholism, due to the decreasing tolerance, could cause fatal TSAH and pathological changes in cerebral tissues of rats under slight cerebral injury.