The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

Injectable ChitHCl-DDA tissue adhesive with high adhesive strength and biocompatibility for torn meniscus repair and regeneration.

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.

Plasma-Enabled Graphene Quantum Dot Hydrogel-Magnesium Composites as Bioactive Scaffolds for In Vivo Bone Defect Repair.

Bioactive and mechanically stable metal-based scaffolds are commonly used for bone defect repair. However, conventional metal-based scaffolds induce nonuniform cell growth, limiting damaged tissue restoration. Here, we develop a plasma nanotechnology-enhanced graphene quantum dot (GQD) hydrogel-magnesium (Mg) composite scaffold for functional bone defect repair by integrating a bioresource-derived nitrogen-doped GQD (NGQD) hydrogel into the Mg ZK60 alloy. Each scaffold component brings major synergistic advantages over the current alloy-based state of the art, including (1) mechanical support of the cortical bone and calcium deposition by the released Mg2+ during degradation; (2) enhanced uptake, migration, and distribution of osteoblasts by the porous hydrogel; and (3) improved osteoblast adhesion and proliferation, osteogenesis, and mineralization by the NGQDs in the hydrogel. Through an in vivo study, the hybrid scaffold with the much enhanced osteogenic ability induced by the above synergy promotes a more rapid, uniform, and directional bone growth across the hydrogel channel, compared with the control Mg-based scaffold. This work provides insights into the design of multifunctional hybrid scaffolds, which can be applied in other areas well beyond the demonstrated bone defect repair.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy.

BACKGROUND: The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC) is a common clinical concern. AIM: To analyse the prognostic factors of overall survival (OS) in patients with unresectable HCC who received conversion therapy. METHODS: One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort (n = 120) and a validation cohort (n = 30). Using the independent risk factors in the training cohort, a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection. The nomogram was internally validated with the bootstrapping method. The predictive performance of nomogram was assessed by Harrell's concordance index (C-index), calibration plot and time-dependent receiver operating characteristic curves and compared with six other conventional HCC staging systems. RESULTS: Multivariate Cox analysis identified that albumin, blood urea nitrogen, gamma-glutamyl transpeptidase to platelet ratio, platelet to lymphocyte ratio, macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model. The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS, which were higher than those of the six conventional HCC staging systems (0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort). The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS. Decision curve analyses indicated satisfactory clinical utility. With a total nomogram score of 196, patients were accurately classified into low-risk and high-risk groups. Furthermore, we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/. CONCLUSION: The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy, which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Fabrication of cellulose derivative coated spherical covalent organic frameworks as chiral stationary phases for high-performance liquid chromatographic enantioseparation.

Porous spherical silica-based chiral stationary phases (CSPs) have been commercially used in the field of chiral separation, however, the scope of their application is, to some extent, limited by the instability of silica towards mobile phase containing strong base or acid. As such, developing new matrix-based CSPs is one of the effective strategies to overcome this bottleneck in studies of chiral separation materials. In this work, we have demonstrated that stable spherical covalent organic frameworks (SCOFs) can be utilized as matrixes for the fabrication of new CSPs for the first time. Specifically, a porous imine-linked SCOF with good crystallinity, large surface area, and high chemical stability is synthesized at room temperature. Then, cellulose-tris (3,5-dimethylphenylcarbamate) (CDMPC), a typical cellulose derivative, is selected as a potential chiral selector and coated onto the robust SCOFs, giving rise to the fabrication of new CDMPC@SCOF CSPs. The as-synthesized stable SCOF-based CSPs are exploited for high-performance liquid chromatographic (HPLC) enantioseparation, showing high resolution abilities for the separation of racemic compounds such as metalaxyl, 1-(1-naphthalenyl)ethanol, epoxiconazol, trans-stilbene oxide, and so on. Moreover, the prepared SCOF-based CSPs exhibit more superior acid and base stability than those of the silica-based CSPs. Our work not only uncovers the great potential of SCOFs as matrixes for constructing novel CSPs, but also expands the application of COFs in the field of enantiomeric separation under harsh base and acid conditions.

Association between 3D Printing-Assisted Pelvic or Acetabular Fracture Surgery and the Length of Hospital Stay in Nongeriatric Male Adults.

Pelvic and acetabular fractures are challenging for orthopedic surgeons, but 3D printing has many benefits in treating these fractures and has been applied worldwide. This study aimed to determine whether 3D printing can shorten the length of hospital stay (LHS) in nongeriatric male adult patients with these fractures. This is a single-center retrospective study of 167 nongeriatric male adult participants from August 2009 to December 2021. Participants were divided into two groups based on whether they received 3D printing assistance. Subgroup analyses were performed. Pearson's correlation and multivariable linear regression models were used to analyze the LHS and the parameters. Results showed that 3D printing-assisted surgery did not affect LHS in the analyzed patients. The LHS was positively correlated with the Injury Severity Score (ISS). Initial hemoglobin levels were negatively associated with LHS in patients aged 18−40 and non-major trauma (ISS < 16) patients. In 40−60-year-old and non-major trauma patients, the duration from fracture to admission was significantly associated with LHS. This study indicates that 3D-assisted technology for pelvic or acetabular fracture surgery for nongeriatric male adults does not influence the LHS. More importantly, the initial evaluation of patients in the hospital was the main predictor of the LHS.

Advances in Multi-Omics Study of Prognostic Biomarkers of Diffuse Large B-Cell Lymphoma.

As the most common subtype of non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL) is characterized by a huge degree of clinical and prognostic heterogeneity. Currently, there is an urgent need for highly specific and sensitive biomarkers to predict the therapeutic response of DLBCL and assess which patients can benefit from systemic chemotherapy to help develop more precise therapeutic regimens for DLBCL. Systems biology (holistic study of diseases) is more comprehensive in quantifying and identifying biomarkers, helps addressing major biological problems, and possesses high accuracy and sensitivity. In this article, we provide an overview of research advances in DLBCL prognostic biomarkers made using the multi-omics approach of genomics, transcriptomics, epigenetics, proteomics, metabonomics, radiomics, and the currently developing single-cell technologies.

Using Cu as a Spacer to Fabricate and Control the Porosity of Titanium Zirconium Based Bulk Metallic Glass Foams for Orthopedic Implant Applications.

In this study, a porous titanium zirconium (TiZr)-based bulk metallic foam was successfully fabricated using the Cu spacer by employing the hot press method. TiZr-based bulk metallic foams with porosities ranging from 0% to 50% were fabricated and analyzed. The results indicate that thermal conductivity increased with the addition of Cu spacer; the increased thermal conductivity reduced the holding time in the hot press method. Moreover, the compressive strength decreased from 1261 to 76 MPa when the porosity of the TiZr-based bulk metallic foam increased to 50%, and the compressive strength was predictable. In addition, the foam demonstrated favorable biocompatibility in cell viability, cell migration capacity, and calcium deposition tests. Moreover, the pore size of the porous TiZr-based bulk metallic foam was around 120 µm. In conclusion, TiZr-based bulk metallic foam has favorable biocompatibility, mechanical property controllability, and porous structure for bone ingrowth and subsequent enhanced osteointegration. This porous TiZr-based bulk metallic foam has great potential as an orthopedic implant to enhance bone healing and decrease healing time.

Does 3D Printing-Assisted Acetabular or Pelvic Fracture Surgery Shorten Hospitalization Durations among Older Adults?

Acetabular or anterior pelvic ring fractures are rare but extremely complicated and challenging injuries for orthopedic trauma surgeons. Three-dimensional (3D) printing technology is widely used in the management of these two fracture types for surgical benefits. Our study aimed to explore whether 3D printing-assisted acetabular or pelvic surgery is beneficial in terms of shortening the length of hospital stay (LHS) and intensive care unit (ICU) stay (ICU LS) for older patients. This retrospective study included two groups of 76 participants over 60 years old who underwent operations with (n = 41) or without (n = 35) guidance by 3D printing. The Mann-Whitney U test was used to analyze continuous variables. Chi-square analysis was applied for categorical variables. Univariable and multivariable linear regression models were used to analyze the factors associated with LHS. The median LHS in the group without 3D printing assistance was 16 (12-21) days, and the median ICU LS was 0 (0-2) days. The median LHS in the group with 3D printing assistance was 17 (12.5-22.5) days, and the median ICU LS was 0 (0-3) days. There was no significant difference in LHS associated with 3D printing assistance vs. that without 3D printing among patients who underwent open reduction and internal fixation for pelvic or acetabular fractures. The LHS positively correlated with the ICU LS whether the operation was 3D printing assisted or not. For fracture surgery in older patients, in addition to the advancement of surgical treatment and techniques, medical teams require more detailed preoperative evaluations, and more personalized medical plans regarding postoperative care to achieve the goals of shortening LHS, reducing healthcare costs, and reducing complication rates.

Two-Step Approach Using Degradable Magnesium to Inhibit Surface Biofilm and Subsequently Kill Planktonic Bacteria.

Bacterial infection remains a great risk in medical implantation surgery. In this paper, we found that degradable metals may be a feasible alternative option of antibacterial implantation materials. It is known that the spalling mechanism of magnesium (Mg) during degradation leads to Mg ions-induced alkaline environment, which is harmful to planktonic bacteria. In this study, we showed that alkaline pH environment is almost harmless to those adhesive bacteria protected in well-formed biofilms. Moreover, experimental results demonstrated that the biofilm formed in the place where Mg spalls are destroyed, releasing the covered bacteria to be planktonic in the alkaline environment. As a result, the colonization of biofilms continues to shrink during the degradation of Mg. It implies that if degradable metal is employed as implantation material, even if bacterial infection occurs, it may be possibly cured without second surgery.

Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Non-anatomic repair of medial meniscus posterior root tears to the posterior capsule provided favourable outcomes in middle-aged and older patients.

PURPOSE: To describe a non-anatomic arthroscopic all-inside repair technique for middle-aged and older patients with medial meniscus posterior root tears (MMPRTs) and to evaluate the short- to mid-term clinical and radiologic results. The hypothesis was that this procedure would yield good clinical outcome results and structural healing in middle- and older-aged patients. METHODS: This was a retrospective study evaluating patients who had undergone MMPRT repair by suturing the meniscal root directly to the capsule, rather than by the transtibial technique, between 2013 and 2016. This all-inside repair technique was performed for patients with type II MMPRTs who were over 40 years old. Exclusion criteria included tibial osteotomy due to malalignment, concomitant multiple-ligament injuries and follow-up time less than 2 years. The Lysholm score, Tegner activity score and International Knee Documentation Committee (IKDC) score were evaluated preoperatively and at the final follow-up. Medial meniscal extrusion, the International Cartilage Repair Society (ICRS) grades of the medial compartment, and the healing status of the medial meniscus root were assessed on magnetic resonance imaging preoperatively and at the final follow-up. RESULTS: Twenty-nine patients (mean age 61.7 ± 7.9) were included; the mean follow-up duration was 46.2 ± 7.9 months. The mean Lysholm score significantly improved from 33.7 ± 20.9 preoperatively to 81.7 ± 19.9 at the final follow-up (p < 0.001), the median Tegner activity score improved from 1.0 (range 1-4) to 3.0 (range 2-4, p < 0.001), and the mean IKDC score improved from 20.1 ± 16.4 to 69.6 ± 16.2 (p < 0.001). On MRI, 9 (31%) cases had complete healing; 17 (59%) had partial healing; and 3 (10%) had failed healing (ICCs ≥ 0.92). Mean meniscal extrusion significantly increased from 2.3 ± 1.7 mm preoperatively to 3.5 ± 1.5 mm postoperatively (p < 0.001, ICCs ≥ 0.92). CONCLUSION: Non-anatomic arthroscopic all-inside repair of MMPRTs to the posterior capsule yielded good to excellent clinical results and a high rate of healing in the medial meniscus root on MRI in middle-aged and older patients at short- to mid-term follow-up, despite increased meniscal extrusion. This method is an alternative to the transtibial pullout repair technique for treating MMPRTs in middle- and older-aged patients. LEVEL OF EVIDENCE: Level IV.

Large-Pore Platelet-Rich Fibrin with a Mg Ring to Allow MC3T3-E1 Preosteoblast Migration and to Improve Osteogenic Ability for Bone Defect Repair.

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.

Transcriptome Analysis Reveals Novel Genes Associated with Cartilage Degeneration in Posttraumatic Osteoarthritis Progression.

OBJECTIVE: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. DESIGN: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. RESULTS: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules-Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. CONCLUSIONS: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.

Biomechanical comparison of four tibial fixation techniques for meniscal root sutures in posterior medial meniscus root repair: A porcine study.

OBJECTIVE: This study hypothesized that the suture anchor of tibial fixation method of PMMR repair technique is the main factor which reduce the gap formation or over displacement of tear site in initial healing, and then investigated the fixation stability of 4 different tibial fixations through cyclic and ultimate failure load testing of meniscal root sutures. METHODS: Twenty-four porcine tibiae with intact medial meniscus roots were randomly assigned into 4 groups: transosseous suture, washer, suture anchor, or screw with washer. Each sample underwent cyclic loading followed by a load-to-failure test. Displacement, maximum load to failure, stiffness, and elongation at failure load were recorded. RESULTS: The maximum average load and displacement at failure for each of the repair groups were as follows: transosseous suture, 232.8 N and 12.16 mm; washer, 189.9 N and 21.5 mm; suture anchor, 140.6 N and 13.8 mm; and screw with washer, 167.9 N and 18.9 mm. The maximum stiffness values for each of the repair groups were as follows: transosseous suture, 19.5 ± 0.7 N/mm; washer, 21.5 ± 1.4 N/mm; suture anchor, 13.8 ± 0.7 N/mm; and screw with washer, 18.9 ± 3.9 N/mm. The mean elongation across the repairs for each of the repair groups after 1000 loading cycles was: transosseous suture, 3.74 ± 0.28 mm; washer, 3.04 ± 0.13 mm; suture anchor, 2.25 ± 0.33 mm; and screw with washer, 2.43 ± 0.19 mm. The mean elongation was significantly less with the suture anchor than with the other techniques (p < .05). CONCLUSION: Under physiological loading, our results indicate that a slower rehabilitation program with limited flexion and only partial weight bearing is advised when using a suture anchor because of the lower maximum load and stiffness. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Tibial fixation using a washer or a screw with a washer is an effective and cost-saving technique when an option is required with high stiffness and low displacement at failure.

Pseudoaneurysm following hamstring tendon harvest in arthroscopic anterior cruciate ligament reconstruction: a case report.

BACKGROUND: Vascular injury is a very rare complication following arthroscopic knee surgery. This is the first report of pseudoaneurysm at the saphenous branch of the descending genicular artery complicating semitendinosus tendon harvest in arthroscopic anterior cruciate ligament reconstruction. CASE PRESENTATION: A 19-year-old male had developed large ecchymosis, focal swelling and tenderness around his posteromedial knee after an arthroscopic anterior cruciate ligament reconstruction. Compartment syndrome of the lower leg and deep vein thrombosis were ruled out. A pseudoaneurysm formation was confirmed through an angiography and coil embolization was performed. At one year follow up, the patient reported improved functional outcome with good stability of the knee. However, mild paresthesia over the posteromedial calf was noted due to the compression injury of the saphenous nerve by the hematoma. CONCLUSIONS: The pseudoaneurysm was presumed to result from accidental vascular injury while dissecting the accessory bands of the semitendinosus and was successfully treated by coil embolization. Care must be taken to section the expansions of the hamstring tendon, especially when the patient presents with underlying coagulopathy or vascular disease.

γ-Mangostin isolated from Garcinia mangostana L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p/IL-6/NF-κB signaling.

Osteoarthritis (OA) a disease associated with joints and become severe with age, due to softening, inflammation and degradation of cartilage in joints. The agents that can target OA is needed, specifically without any side effects. Garcinia mangostana L. (Mangosteen) a tropical fruit used to treat many skin and stomach associated ailments. γ- Mangostin (γ-MS) a key bioactive substance present in mangosteen. Here, we aimed to explore γ-MS potential in targeting the pro-inflammatory cytokine, factors and miRs in OA progression. Significantly, γ-MS suppresses the inflammatory cytokines (IL-6, TNF-α, and INF- γ) and factors (NF-κB, STAT3, and COX-2) which regulates/participate in the catabolic process of cartilage destruction. Result of Hematoxylin-eosin (H&E) staining of tissue sections of OA joints of γ-MS treated and non-treated mice confirm γ-MS improves the signs of injuries, and maintains the structural integrity of the articular cartilage (epiphyseal disk joints and bone marrow) and reduces inflammation. Mechanistically, γ-MS targets miR-98-5p and miR-124-3p which are found to suppress the expression IL-6 and NF-κB, respectively. But in OA these miRs are inhibited, especially miR-124-3p which regulates not only NF-κB but also TNF-α, IL-6 and MMP7. With a further investigation underway, γ-MS represents an important source for treating and managing OA.