The novel DNA methylation marker FIBIN suppresses non-small cell lung cancer metastasis by negatively regulating ANXA2.

OBJECTIVES: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. METHODS: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. RESULTS: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of ß-catenin by reducing the binding activity of GSK3ß with ANXA2 while promoting interaction between GSK3ß and ß-catenin. CONCLUSION: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.

An observation study of the effect of "Internet + Nursing" on psychological status and quality of life of patients with thyroid eye disease.

"Internet + Nursing" refers to medical institutions using Internet technologies and big data to provide nursing services to discharged patients or those with severe illnesses unable to visit hospitals, through online applications and offline care provision. This study aimed to explore the influence of "Internet + Nursing" on the psychological status and quality of life of patients with thyroid eye disease. Sixty-eight patients with thyroid eye disease from January 2021 to December 2022 were divided into a research group (n = 34, joined the platform) and control group (n = 34, not joined the platform) based on their voluntary participation in our hospital's "Internet + Nursing Platform." The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < .05). The short form-36 health survey (SF-36) scores in various dimensions were higher in the research group compared to the control group (P < .05). The incidence rates of retinal detachment, vitreous hemorrhage, diabetic retinopathy, and iris neovascularization were lower in the research group compared to the control group (P < .05). After nursing, exophthalmos, blink frequency, and eyelid height of the research group were lower than those of the control group, while tear film breakup time was higher than that of the control group (P < .05). The visual acuity of the research group was higher than that of the control group (P < .05). After nursing, the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) scores in various dimensions were significantly higher in the research group than those in the control group (P < .05). Additionally, after nursing, the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the research group were lower than those in the control group (P < .05). The patients in the research group exhibited higher recognition scores of nursing compared to those in the control group (P < .05). Through the implementation of "Internet + Nursing" for patients with thyroid eye disease discharged from our hospital, we can provide better out-of-hospital nursing for patients, reduce the occurrence of complications, improve ocular surface symptoms, promote visual acuity recovery, and improve patients' psychological status and quality of life.

Better clinical outcomes and return to sport rates with additional medial meniscus root tear repair in high tibial osteotomy for medial compartmental knee osteoarthritis.

PURPOSE: This retrospective study aimed to investigate whether the repair of medial meniscus posterior root tears (MMPRTs) is effective for improving clinical outcomes and return to sports rates in young patients (50 years old or younger) with medial compartment knee osteoarthritis (KOA) and MMPRTs. METHODS: Between 2016 and 2019, 153 patients with KOA and MMPRTs who underwent open-wedge high tibial osteotomy (OWHTO) were retrospectively included. The patients were divided into OWHTO combined with MMPRT repair (n = 73) and isolated OWHTO (n = 80) groups. Lysholm scores, Hospital for Special Surgery (HHS) scores, Tegner scores, flexion contracture, range of knee flexion, return to sports rates and postoperative complications were compared. Radiological outcomes, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and Kellgren-Lawrence (K-L) grade, were compared between the two groups. RESULTS: After a mean follow-up of 30.1 ± 3.0 months, the OWHTO + Repair group observed better clinical outcomes compared with the OWHTO group (Lysholm score: 86.7 ± 7.4 vs. 81.6 ± 6.9, p = 0.023. HHS score: 85.4 ± 8.20 vs. 80.5 ± 7.1, p = 0.039). The OWHTO + Repair group had higher Tegner scores and return to sports rates than the OWHTO group (Tegner score: 6 vs. 5, p = 0.020; return to sports rates: 38% vs. 15%, p = 0.001). No fracture or major complications occurred. Radiological outcomes showed no significant differences between the two groups (HKA: 181.1 ± 2.7 vs. 180.1 ± 1.5 n.s; MPTA: 90.1 ± 1.8 vs. 89.2 ± 1.4, n.s; JLCA:1.9 ± 0.7 vs. 2.1 ± 0.7, n.s). CONCLUSIONS: Additional MMPRT repair during OWHTO was associated with better clinical outcomes and higher rates of return to sports in young patients with medial compartment KOA and MMPRTs. LEVEL OF EVIDENCE: Level III.

The podoplanin-CLEC-2 interaction promotes platelet-mediated melanoma pulmonary metastasis.

BACKGROUND: Podoplanin (PDPN) expressed on tumour cells interacts with platelet C-type lectin-like receptor 2 (CLEC-2). This study aimed to investigate the role of the PDPN-platelet CLEC-2 interaction in melanoma pulmonary metastasis. METHODS: Murine melanoma B16-F0 cells, which have two populations that express podoplanin, were sorted by FACS with anti-podoplanin staining to obtain purified PDPN + and PDPN- B16-F0 cells. C57BL/6J mice transplanted with CLEC-2-deficient bone marrow cells were used for in vivo experiments. RESULTS: The in vivo data showed that the number of metastatic lung nodules in WT mice injected with PDPN + cells was significantly higher than that in WT mice injected with PDPN- cells and in WT or CLEC-2 KO mice injected with PDPN- cells. In addition, our results revealed that the platelet Syk-dependent signalling pathway contributed to platelet aggregation and melanoma metastasis. CONCLUSIONS: Our study indicates that the PDPN-CLEC-2 interaction promotes experimental pulmonary metastasis in a mouse melanoma model. Tumour cell-induced platelet aggregation mediated by the interaction between PDPN and CLEC-2 is a key factor in melanoma pulmonary metastasis.

Comparison of the Clinical Outcomes between All-inside and Standard Technique in Anterior Cruciate Ligament Reconstruction with 6-strand Hamstring Tendon Autograft.

OBJECTIVE: All-inside and standard techniques with 4-strand hamstrings graft have been widely used in anterior cruciate ligament (ACL) reconstruction. However, the graft diameter of less than 8 mm will significantly increase the rate of surgical failure, and the 6-strand graft can solve this problem. The purpose of this study is to compare all-inside ACL reconstruction using suspensory cortical button fixation on both tibia and femur with standard ACL reconstruction using suspensory femoral fixation and a bioabsorbable tibial interference screw with a 6-strand hamstring tendon autograft in postoperative clinical outcomes. METHODS: From January 2020 to December 2020, 48 patients performed ACL reconstruction were divided into the all-side group and the standard group according to the different surgical techniques. Magnetic resonance imaging (MRI) and subjective function scores was used to assess clinical outcomes at least 24 months following ACL reconstruction. MRI was used to measure the value of bone tunnel widening in articular and middle portions. Subjective function scores included the Lysholm knee score, the International Knee Documentation Committee (IKDC) score, the Knee Society Score (KSS) for pain and function, and KT-1000. The t-test was used assuming the distribution of the patients which follows the normal distribution and we used non-parametric tests if these two conditions were not satisfied. RESULTS: At the final follow-up, there were 22 patients in the all-inside group and 24 patients in the standard group. No significant differences were found with respect to femoral tunnel widening and subjective function scores. However, a significant increase in tibial tunnel widening was found in the middle portion of the standard group (2.25 ± 0.74) compared to the all-inside group (0.76 ± 0.24) (p < 0.01) and also in the articular portion of the standard group (2.07 ± 0.77) compared to the all-inside group (1.52 ± 0.54) (p = 0.02). In addition, the value of the KT-1000 was 1.81 ± 0.45 for the all-inside group and 2.12 ± 0.44 in the standard group (p = 0.016). CONCLUSION: The objective stability of the knee was relatively better in the all-inside group than in the standard group. And tunnel widening after ACL reconstruction was significantly greater in the standard technique when compared to the all-inside technique on the tibia side.

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.

Designing a bi-layer multifunctional hydrogel patch based on polyvinyl alcohol, quaternized chitosan and gallic acid for abdominal wall defect repair.

In abdominal wall defect repair, surgical site infection (SSI) remains the primary cause of failure, while complications like visceral adhesions present significant challenges following patch implantation. We designed a Janus multifunctional hydrogel patch (JMP) with antibacterial, anti-inflammatory, and anti-adhesive properties. The patch comprises two distinct layers: a pro-healing layer and an anti-adhesion layer. The pro-healing layer was created by a simple mixture of polyvinyl alcohol (PVA), quaternized chitosan (QCS), and gallic acid (GA), crosslinked to form PVA/QCS/GA (PQG) hydrogels through GA's self-assembly effect and hydrogen bonding. Additionally, the PVA anti-adhesive layer was constructed using a drying-assisted salting method, providing a smooth and dense physical barrier to prevent visceral adhesion while offering essential mechanical support to the abdominal wall. The hydrogel patch demonstrates widely adjustable mechanical properties, exceptional biocompatibility, and potent antimicrobial properties, along with a sustained and stable release of antioxidants. In rat models of skin and abdominal wall defects, the JMP effectively promoted tissue healing by controlling infection, inhibiting inflammation, stimulating neovascularization, and successfully preventing the formation of visceral adhesions. These compelling results highlight the JMP's potential to improve the success rate of abdominal wall defect repair and reduce surgical complications.

Morphological Changes of the Posterior Femoral Condyle After Medial Patellar Retinaculum Plasty in Skeletally Immature Patients With Recurrent Patellar Dislocation and Trochlear Dysplasia.

Background: Surgical correction for recurrent patellar dislocation (RPD) can improve femoral trochlear morphology; nonetheless, the effects of surgical correction on femoral condyle morphology are unclear. Purpose: To investigate the morphological changes in the posterior femoral condyle in skeletally immature patients with RPD and trochlear dysplasia (TD) after surgical correction. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 20 skeletally immature patients with bilateral RPD and TD were included in this study. For each patient, the knee that was dislocated more frequently or had sustained a recent injury was treated with medial patellar retinaculum plasty (group S; n = 20 knees), and the asymptomatic or only occasionally dislocated contralateral knee was treated conservatively (group C; n = 20 knees). The lengths of the anterior medial and lateral femoral condyles and the lengths of the posterior medial and lateral femoral condyles were evaluated preoperatively and at the final follow-up. Trochlear morphological characteristics, tibial tuberosity-trochlear groove distance, and patellar tilt angle were compared between preoperative and final follow-up values with the 2-sample paired Student t test and were compared between groups S and C with the independent-samples t test. Results: The mean follow-up time was 60.7 ± 4.8 months. No knee in group S experienced a redislocation, whereas 80% (16/20) of knees in group C experienced a dislocation. There were significant group differences in the ratio of the posterior medial femoral condyle (PMFC) to the posterior lateral femoral condyle (PLFC) (group S, 1.08 ± 0.05; group C, 1.14 ± 0.06; P = .042). There was no significant difference in the ratio of the anterior lateral femoral condyle to the anterior medial femoral condyle (group S, 1.16 ± 0.13; group C, 1.18 ± 0.09; P = .635). In group S, all trochlear morphological characteristics and patellofemoral joint characteristics improved compared with preoperatively (P≤ .047 for all). In addition, all values significantly differed between groups S and C at the final follow-up (P≤ .044 for all). Conclusion: The study findings demonstrated that the morphology of the posterior femoral condyle in skeletally immature patients with bilateral RPD and TD changes after surgical correction, with the PLFC growing faster than the PMFC.

Ginsenoside Rg1 attenuates lipopolysaccharide-induced chronic liver damage by activating Nrf2 signaling and inhibiting inflammasomes in hepatic cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. AIM OF THE STUDY: Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 µg/kg) for 21 days. Serum liver function indicators and levels of IL-1ß, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. RESULTS: Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1ß, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1ß and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. CONCLUSION: The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells.

Overexpression of NDRG1 leads to poor prognosis in hepatocellular carcinoma through mediating immune infiltration and EMT.

BACKGROUND: NDRG1, the first member of the NDRG family, is a multifunctional protein associated with carcinogenesis. Its function in human cancer is currently poorly understood. The aim of this study was to explore the importance of NDRG1 in tumor immune cell infiltration and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. METHODS: NDRG1 expression in various cancers was analyzed using TIMER 2.0, the Human Protein Atlas (HPA), UALCAN and PrognoScan. Wound healing, Transwell, MTT and colony formation assays were performed to confirm the effects of NDRG1 on the metastasis and proliferation of HCC cells. Western blotting was used to study the effect of NDRG1 on the expression of EMT-related proteins. Signaling networks were constructed using LinkedOmics and Metascape. TIMER2.0 and TISIDB were used for comprehensive analysis of tumor-infiltrating immune cells and tumor-infiltrating lymphocytes (TILs). RESULT: NDRG1 expression was higher in HCC tissue than in normal liver tissue at both the mRNA and protein levels. Overexpression of NDRG1 is associated with poor prognosis in HCC patients. Genomic analysis suggests that NDRG1 promoter hypermethylation leads to enhanced transcription, which may be one mechanism for NDRG1 upregulation in HCC. The overexpression of NDRG1 promotes the invasion, migration, and proliferation of HCC cells and induces the expression of EMT-related proteins. Immunoinfiltration analysis suggests that NDRG1 is involved in the recruitment of immune cells. CONCLUSIONS: The present study showed that NDRG1 may induce metastasis and invasion through EMT and immune cell infiltration. NDRG1 could be used as a biomarker for the diagnosis and prognosis of HCC and could be a potential therapeutic target in HCC.

Immunological studies on acupuncture and moxibustion treatment of rheumatoid arthritis: A review.

From the 4 perspectives of T lymphocytes, various cytokines, adenosine and "neuro-endocrine-immune" network, the researches related to the immune mechanism of acupuncture and moxibustion in the treatment of rheumatoid arthritis (RA) in recent years were summarized, and different acupuncture and moxibustion treatments were analyzed. The method has a regulatory effect on the mechanism of RA, in order to provide a reference and basis for acupuncture research on the immune mechanism of RA, and promote the further development of research in this field.

Hierarchically decorated magnetic nanoparticles amplify the oxidative stress and promote the chemodynamic/magnetic hyperthermia/immune therapy.

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.

Effect of pre-infusion of hypertonic saline on postoperative delirium in geriatric patients undergoing shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: Neuroinflammation may be a potential mechanism of postoperative delirium (POD) in geriatric patients, and hypertonic saline (HS) has immunomodulatory properties. The purpose of this study was to investigate whether HS could reduce the incidence of POD in elderly patients and its effect on neutrophil activation and inflammatory cytokine expression. METHODS: We studied the effect of pre-infusion of 4 mL/kg 3% hypertonic saline vs. 4 mL/kg 0.9% normal saline on POD in patients undergoing shoulder arthroscopy in a prospective, randomized, double-blind, controlled trial. Neutrophil surface molecules (CD11b, CD66b and CD64) were analyzed by flow cytometry. Circulating concentrations of inflammatory factors IL-1ß, IL-6, TNF-α and neurological damage factor S100ß were assessed by enzyme immunoassay. The Confusion Assessment Method-Chinese Revision (CAM-CR) was applied for the assessment of POD 1-3 days after surgery. RESULTS: The incidence of POD in group H was significantly lower than that in group N (7.14% vs 26.83%, P = 0.036). The expression levels of inflammatory cytokines ( IL-6 and TNF-α) and neutrophil surface markers (CD11b and CD66b) were significantly lower in group H than in group N at 24 h after surgery (P = 0.018, P < 0.001, P < 0.001, P = 0.024). There were no significant differences in postoperative pain, nausea and vomiting, infection, phlebitis, and patients satisfaction between the two groups. CONCLUSION: Pre-infusion of HS can reduce the incidence of POD and the immune-inflammatory response. TRIAL REGISTRATION: Chinese Clinical Trial Registry (14/4/2022, registration number: ChiCTR2200058681.

An alternative negative pressure treatment for enteroatmospheric fistula resulting from small intestinal leakage caused by incision dehiscence.

Background: To investigate the efficacy of an alternative negative pressure treatment for the treatment of enteroatmospheric fistula transformed from small intestinal leakage due to incision dehiscence after abdominal surgery. Methods: Patients with an enteroatmospheric fistula from small intestinal leakage owing to incision dehiscence following abdominal surgery between January 2010 and December 2019 were retrospectively reviewed. Results: A total of 83 patients (mean age: 38.3 ± 11.6 years; Body mass index: 19.9 ± 2.2 kg/m2) were enrolled. Of the 83 patients, 59 (71.1 %) achieved fistula closure. High-output fistula (Hazard ratio = 0.48; 95 % Confidence interval: 0.29-0.81; P = 0.006) and abdominal wall thickness >2 cm (Hazard ratio = 2.76; 95 % Confidence interval: 1.35-5.67; P = 0.006) were identified as factors affecting fistula closure. Lastly, 11/83 (13.3 %) patients exhibited re-dehiscence. Conclusion: Appropriately applying the alternative negative pressure treatment may enable fistula closure in patients with enteroatmospheric fistula resulting from small intestinal leakage caused by incision dehiscence.

How Do the Morphological Abnormalities of Femoral Head and Neck, Femoral Shaft and Femoral Condyle Affect the Occurrence and Development of Medial Knee Osteoarthritis.

OBJECTIVE: At present, the main viewpoint is that tibial varus is the main reason of medial knee osteoarthritis (OA), and high tibial osteotomy (HTO) is also the main alignment correction method to correct medial knee OA. In contrast, the impact of the anatomical alignment of the femur on medial knee OA is often overlooked. We evaluated the increased risk for medial knee OA because a varus alignment could be attributed to the anatomical reasons that include hip anatomy, femoral shaft bowing (FSB) and femoral condylar dysplasia. METHODS: The present research adopted a cross-sectional study method. We selected 62 patients with HTO in the Third Hospital of Hebei Medical University from June 2021 to March 2022 as the HTO group and 55 healthy volunteers as the control group. Femoral neck-shaft angle (NSA), lateral FSB, mechanical lateral distal femoral angle (mLDFA) and hip-knee-ankle (HKA) was radiographically examined within the two groups. The femoral neck length and offset were also measured, and the ratio is represented by the ratio of the femoral neck length to off-set (N/O). The 2-tailed Student t-test was used to compare the differences between groups when the data were in accordance with a normal distribution. Otherwise, the Mann-Whitney U tests was used to compare the differences between groups. RESULT: Compared to the control group, the HTO group had a higher offset (p < 0.05), greater femoral neck length (p < 0.05), and decreased (more varus) NSA (p < 0.05). The HKA in the HTO group was 172.20 ° (3.50°), which was significantly lower than that of the control group 177.00° (3.05°), (p < 0.001), while the medial OA was associated with more varus HKA. The mean mLDFA was 89.10 ° (2.35°) and 87.50° (2.85°) in the HTO and control groups (p < 0.005), respectively. The mean lateral FSB values of the full-length radiographs were larger (p < 0.001) in the HTO group (4.24° ± 3.25°) than that in control group (1.16° ± 2.32°). CONCLUSION: The reduction of NSA (coxa vara) and the increase of the mLDFA can lead to medial knee OA, while the lateral FSB also affects medial OA. We believe that femoral deformity is also one of the cause of the medial knee OA. Therefore, it is necessary to evaluate the joint deformity of the femur and tibia before surgery in order to determine whether to use HTO alone to correct the lower limb alignment.

Analysing the mechanism of food waste anaerobic digestion enhanced by iron oxide in a continuous two-stage process.

The food waste (FW) digestion performance can be enhanced by introducing iron oxide (IO) into digesters. However, the role of IO in continuous two-stage digesters in enhancing the FW anaerobic digestion remains unclear. In this study, the effect of IO on the bioenergy recovery from a two-stage digestion process was investigated. The bioenergy recovery was significantly increased by up to 208.43 % with IO addition. The activities of dehydrogenase, α-amylase, and protease increase by 0.82-1.44, 7.24-14.56 and 7.97-20.45 times, respectively, as compared with that of the blank. With IO addition, the metabolic pathway in hydrolytic-acidogenic (HA) reactor shifted from lactic acid fermentation to butyric fermentation, which promoted stable methane production in methanogenic (MG) reactor. The activity of coenzyme F420 increased by 19.19-39.01 times, indicating that IO facilitated FW digestion by promoting hydrogenotrophic methanogenesis. The enhancement in the enzyme activity was attributable to the Fe2+ generated by dissimilatory iron reduction. According to the microbial analysis, IO enhanced interspecies hydrogen transfer between Methanobacterium and Syntrophomonas. Furthermore, IO improved direct interspecies electron transfer between Geobacter sulfurreducens and Methanosarcina. The effluent recirculation strategy greatly facilitated the hydrolysis and acidification of FW, which was critical for improving the two-stage process performance.

Aminooxyacetic acid hemihydrochloride leads to decreased intracellular ATP levels and altered cell cycle of prostate cancer cells by suppressing energy metabolism.

The second most common cancer among men is prostate cancer, which is also the fifth leading reason for male cancer deaths worldwide. Bone metastases are the main factor affecting the prognosis of prostate cancer. Consequently, antitumor and anti-prostate cancer-induced bone destruction medicines are urgently needed. We previously discovered that aminooxyacetic acid hemihydrochloride (AOAA) suppressed bone resorption and osteoclast growth by decreasing adenosine triphosphate (ATP) production and limiting oxidative phosphorylation (OXPHOS). Here, we evaluated the impacts of AOAA on prostate cancer RM-1 cells in vitro. It's found that AOAA significantly inhibited cell proliferation, migration, and invasiveness, decreased ATP levels, increased ROS, halted the cell cycle phase, and triggered apoptosis. AOAA also decreased mitochondrial membrane potential and the ability to uptake glucose, suggesting that the antitumor effects of AOAA were expressed through the inhibition of OXPHOS and glycolysis. Furthermore, we assessed the effects of AOAA in vivo using a prostate cancer-induced bone osteolysis mice model. AOAA also delayed tumor growth and bone destruction in vivo. On the whole, our findings imply that AOAA may potentially have therapeutic effects on prostate cancer and prostate cancer-induced osteolysis.

[Changes and clinical significance of multiple cytokines in exhaled breath condensate in patients with severe inhalation injury].

OBJECTIVE: To investigate the changes and clinical significance of multiple cytokine levels in exhaled breath condensate (EBC) in patients undergoing tracheotomy with severe inhalation injury. METHODS: A prospective study was conducted. A total of 32 patients with severe burn combined with severe inhalation injury admitted to the department of burns and plastic surgery of Affiliated Suzhou Hospital of Nanjing Medical University from May 2021 to August 2022 were enrolled. Twenty healthy volunteers from the same period were served as controls. EBC of patients at 12 hours after burn and the samples of healthy controls were collected. The levels of 27 cytokines in EBC, including tumor necrosis factor-α (TNF-α) and interleukins (IL-1ß, IL-6, IL-8, IL-10, and IL-17), were determined by liquid phase chip technology. Meanwhile, plasma of patients at 12 hours after burn and the plasma of volunteers were collected, and the levels of inflammatory cytokines were detected by liquid chip technology, and the differences between the levels in plasma and those in EBC were analyzed. Plasma and EBC of patients with aspiration injury were collected at 12 hours and 3, 7, 14 and 21 days after burn, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Finally, 32 patients were enrolled, and the total burned area was (40±16)% of total body surface area (TBSA). The time of admission was (4.2±2.3) hours after injury. (1) Twenty-seven cytokines in EBC: 18 kinds of cytokines including macrophage inflammatory protein-1ß (MIP-1ß), IL-6, IL-5, IL-2, IL-1ß, IL-8, IL-10, IL-15, IL-9, interferon-γ (IFN-γ), IL-1 receptor antagonist (IL-1ra), TNF-α, chemotactic factor for eosinophil (Eotaxin), basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF) were significantly increased in patients with severe aspiration injury compared with health controls. Eotaxin was not detected in EBC of healthy controls. Five cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine ligand 5 (CCL5/RANTES), IL-13, IL-4 and MIP-1α, were not detected in EBC of severe inhalation injury patients and healthy controls. Vascular endothelial growth factor (VEGF) and IL-12 p70 in EBC of severe aspiration injury patients were slightly decreased as compared with healthy controls, while IL-7 and IL-17 were slightly increased, but the differences were not statistically significant. (2) Six inflammatory cytokines in plasma: the levels of IL-6 and IL-8 in the severe aspiration injury group were significantly increased as compared with healthy controls [IL-6 (ng/L): 18.51 (10.87, 26.21) vs. 0.22 (0.10, 0.36), IL-8 (ng/L): 10.75 (8.58, 18.79) vs. 1.06 (0.81, 2.14), both P < 0.01]. The plasma levels of TNF-α, IL-1ß and IL-10 were slightly increased in patients with severe aspiration injury as compared with healthy controls, and IL-17 was slightly decreased, but the difference was not statistically significant. In the EBC collected during the same period, five inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8 and IL-10, in patients with severe inhalation injury were significantly increased as compared with healthy controls [TNF-α (ng/L): 16.42 (12.57, 19.21) vs. 7.34 (6.11, 8.69), IL-1ß (ng/L): 15.57 (10.53, 20.25) vs. 0.99 (0.67, 1.41), IL-6 (ng/L): 13.36 (9.76, 16.54) vs. 0.70 (0.42, 0.85), IL-8 (ng/L): 1 059.29 (906.91, 1 462.37) vs. 10.36 (8.40, 12.37), IL-10 (ng/L): 2.69 (1.54, 3.33) vs. 1.54 (1.18, 2.06), all P < 0.05]. (3) Dynamic changes of TNF-α in plasma and EBC: the level of TNF-α in EBC of patients with severe aspiration injury was lower than that in plasma. Plasma TNF-α level was increased gradually with the extension of time after injury, and was significantly higher than that of healthy controls on day 3 [ng/L: 30.38 (24.32, 39.19) vs. 22.94 (17.15, 30.74), P < 0.05], and reached the peak on day 14, then fell back. The level of TNF-α in EBC at 12 hours after injury was significantly higher than that in healthy controls [ng/L: 15.34 (11.75, 18.14) vs. 6.99 (6.53, 7.84), P < 0.01], and reached the peak on 3 days after injury, and then gradually decreased. CONCLUSIONS: There are changes in the expression of multiple cytokines in EBC of patients with severe inhalation injury, and the changes of many inflammatory cytokines including TNF-α are more sensitive than those in plasma, which can be used to monitor and evaluate the condition of patients with inhalation injury.

Prediction of opioid-related outcomes in a medicaid surgical population: Evidence to guide postoperative opiate therapy and monitoring.

BACKGROUND: Treatment of surgical pain is a common reason for opioid prescriptions. Being able to predict which patients are at risk for opioid abuse, dependence, and overdose (opioid-related adverse outcomes [OR-AE]) could help physicians make safer prescription decisions. We aimed to develop a machine-learning algorithm to predict the risk of OR-AE following surgery using Medicaid data with external validation across states. METHODS: Five machine learning models were developed and validated across seven US states (90-10 data split). The model output was the risk of OR-AE 6-months following surgery. The models were evaluated using standard metrics and area under the receiver operating characteristic curve (AUC) was used for model comparison. We assessed calibration for the top performing model and generated bootstrap estimations for standard deviations. Decision curves were generated for the top-performing model and logistic regression. RESULTS: We evaluated 96,974 surgical patients aged 15 and 64. During the 6-month period following surgery, 10,464 (10.8%) patients had an OR-AE. Outcome rates were significantly higher for patients with depression (17.5%), diabetes (13.1%) or obesity (11.1%). The random forest model achieved the best predictive performance (AUC: 0.877; F1-score: 0.57; recall: 0.69; precision:0.48). An opioid disorder diagnosis prior to surgery was the most important feature for the model, which was well calibrated and had good discrimination. CONCLUSIONS: A machine learning models to predict risk of OR-AE following surgery performed well in external validation. This work could be used to assist pain management following surgery for Medicaid beneficiaries and supports a precision medicine approach to opioid prescribing.

Pteryxin suppresses osteoclastogenesis and prevents bone loss via inhibiting the MAPK/Ca2+ signaling pathways mediated by ROS.

Osteoporosis, as a severe public health problem worldwide, causes systemic damage to bone mass, strength, and microstructure with an increased propensity for fragility fractures. Given the inherent adverse effects associated with long-term use of current prescription medications for osteoporosis treatment, identifying natural alternatives to existing treatment methods is imperative. Pteryxin (PTX), a natural coumarin, is isolated from the Peucedanum species belonging to the family Apiaceae. PTX has been reported to have antioxidant, anti-inflammatory and anti-obesity properties. However, its effect on osteoporosis has not been clarified. Our study confirmed that PTX could attenuate the formation of osteoclasts and bone resorption on a dose-dependent basis in vitro. Consistently, in vivo ovariectomy (OVX)-induced osteoporosis models simulating the physiological characteristics of postmenopausal women showed that PTX could partially reverse the bone loss caused by OVX. Further study of its mechanism revealed that PTX might block the MAPK and Ca2+-calcineurin-NFATc1 signaling pathways by decreasing the reactive oxygen species (ROS) level in osteoclasts to dampen the expression of critical transcriptional NFATc1 and downstream osteoclast-specific genes. Overall, PTX may present a new or alternative treatment option for osteoporosis.