Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Objective:To evaluate the influence of the sleeve lengths and implant lengths on accuracy of static computer-assisted implant surgery (sCAIS).Methods:Twenty-eight models of bilateral mandibular single tooth loss were included. Fifty-five implants were placed under the guidance of sCAIS (Straumann Bone Level 4.1 mm×10 mm). According to the height of metal sleeve of static guide plate, 55 implants were divided into 11 groups (free hand group, 1 mm group, 2 mm group, 3 mm group, 4 mm group, 5 mm group, 6 mm group, 7 mm group, 8 mm group, 9 mm group, 10 mm group), with 5 implants in each group. Eight research models were included. Group with 5 mm sleeve guides were used to place implants of different length, (Straumann Bone Level width 4.1 mm, height was 8 mm, 10 mm and 14 mm), 5 implants in each group. Eighteen patients with mandibular single tooth loss were included in the Department of Oral Implantology, Tianjin Stomatological Hospital from October 2018 to June 2019. There were 10 males and 8 females, 18-46(33.7±7.9) years old. A total of 18 implants were implanted and divided into 3 groups (free hand group, 3 mm group and 5 mm group) with 6 implants in each group. Digital software was used to compare the implant positions before and after implantation. Non-parametric Kruskal-Wallis test or one-way ANOVA were used to analyze the results.Results:There was no significant difference in implant vertical deviation between different sleeve height groups (1-10 mm) and free hand group, but the neck deviation in free hand group[(1.04±0.13) mm] was significantly higher than that in different sleeve height groups (1-10 mm) ( P<0.05). The tip deviations of free hand group, 1 mm group and 2 mm group [(1.32±0.43), (0.83±0.10) and (0.78±0.11) mm, respectively] was significantly higher than that of 10 mm group [(0.31±0.14) mm]( P<0.05). The angle deviation of free hand group and 1 mm group (3.99°±0.85° and 2.59°±0.69°), respectively] was significantly higher than that of 10 mm group (0.61°±0.03°) ( P<0.05). The tip deviations of implants in the 14 mm group [(0.83±0.22) mm] was significantly higher than that in the 8 mm and 10 mm groups [(0.44±0.07) and (0.49±0.06) mm, respectively]. Clinical studies showed that there was no significant difference in neck deviation, tip deviation and angle deviation between 3 mm group and 5 mm group ( P>0.05), but deviations were significantly lower than those in free hand group ( P<0.05). Conclusions:The length of the sleeves has significant influence on the accuracy of the surgical guide. There was no significant difference in accuracy of the implant guide with 3 mm or 5 mm metal sleeves. The vitro study has some limitations and needs further systematic research.

Objective:To explore the training methods and training effects of "2+1" structured training mode to provide references for the training of intravenous therapy professional nurses. nurses specializing in intravenous therapy.Methods:Using prospective non-random self-controlled research methods, a total of 39 trainees from municipal and county-level hospitals who received 5 phases of training of intravenous therapy professional nurses in Mianyang Central Hospital in Sichuan Province from March 2016 to March 2018 were selected as the research objects. According to the questionnaire of students' needs, the matching of tutors' subspecialty direction was carried out. The training was carried out in accordance with the "2+1" structured training mode of 2 months of centralized training and 1 year of follow-up, guidance and tracking by tutors. Theoretical and specialized technical test scores before and after training were compared and the completion rate of their training needs was also analyzed.Results:The theoretical test scores and technical operation scores of venous indwelling needle and venous catheter maintenance of intravenous therapy professional nurse trainees after training were respectively (97.05±1.39) and (95.87±2.45) , which were higher than (62.60±6.33) and (66.38±8.09) before training. The differences were statistically significant ( P<0.05) . After 1 year of follow-up, tracking and guidance, the rate of achieving the "training needs" by the trainees was 90.30%. Of the 39 trainees, 38 nurses continued to work as clinical intravenous therapy professional nurses and the rate of professional nurses engaged in clinical intravenous therapy was 97.4%. Conclusions:"2+1" structured training mode is to cultivate practical intravenous therapy professional nurses oriented by job requirements, improve the professional quality of intravenous therapy professional nurses and promote the harmonization of training and use of intravenous therapy professional nurses.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.

To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
 Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
 Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
 Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
Animals ; Disease Models, Animal ; Doxorubicin ; Glomerulosclerosis, Focal Segmental ; chemically induced ; Kidney ; drug effects ; Mice ; Mice, Inbred NOD ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Xanthones ; pharmacology ; therapeutic use

Objective To study the correlations among lumbosacral anatomical structure variations and herniation of intervertebral disc.Methods Through analyzing lumbar CT images of 684 patients with lumbocrural pain between 15 to 24 years old, the anatomical variations of spondylolysis, scoliosis deformity, lumbosacral transitional vertebra, subfissure, lumbosacral angle and others (including vertebral muscles beside, spines, transverse process on both sides) were observed, and the correlations among these anatomical variations and herniation of intervertebral disc were analyzed.Results The correlations among these above mentioned anatomical variations and herniation of intervertebral disc were 93.6%,92.3%,87.5%,81.3%,72.1%,53.3% respectively.In 91.4% of patients, the lumbosacral anatomical structure variations suffered herniation of intervertebral disc at the same time.But only 36.2% of patients suffered herniation of intervertebral disc without lumbosacral anatomical structure variations.Conclusion Lumbosacral anatomical structure variation is the main reason of herniation of intervertebral disc on teenagers.CT examination,which can reflect the correlation between them.