The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Multifunctionalized Covalent Organic Frameworks for Broad-Spectrum Extraction and Ultrasensitive Analysis of Per- and Polyfluoroalkyl Substances.

The contamination of surface and ground water by per- and polyfluoroalkyl substances (PFASs) has become a growing concern, and the structural diversity of PFASs is the major challenge for their ubiquitous applications. Strategies for monitoring coexistent anionic, cationic, and zwitterionic PFASs even at trace levels in aquatic environments are urgently demanded for effective pollution control. Herein, novel amide group and perfluoroalkyl chain-functionalized covalent organic frameworks (COFs) named COF-NH-CO-F9 are successfully synthesized and used for highly efficient extraction of broad-spectrum PFASs, attributing to their unique structure and the multifunctional groups. Under the optimal conditions, a simple and high-sensitivity method is established to quantify 14 PFASs including anionic, cationic, and zwitterionic species by coupling solid-phase microextraction (SPME) with ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) for the first time. The established method displays high enrichment factors (EFs) of 66-160, ultrahigh sensitivity with low limits of detection (LODs) of 0.0035-0.18 ng L-1, a wide linearity of 0.1-2000 ng L-1 with correlation coefficient (R2) ≥0.9925, and satisfactory precision with relative standard deviations (RSDs) ≤11.2%. The excellent performance is validated in real water samples with recoveries of 77.1-108% and RSDs ≤11.4%. This work highlights the potential of rational design of COFs with the desired structure and functionality for the broad-spectrum enrichment and ultrasensitive determination of PFASs in real applications.

A flexible electrochemical glucose sensing platform based on an electrospun PVA mat covered with in situ grown silver nanoparticles and a mixed self-assembled monolayer of glucose oxidase and ferrocene.

An electrochemical glucose sensor based on flexible materials is significant for wearable devices used for real-time health monitoring and diagnosis. However, applying flexible electrodes involves complex fabrication processes and might reduce detection sensitivity. To overcome these obstacles, we herein report a novel strategy for preparing a highly flexible enzyme electrode based on an electrospun poly(vinyl alcohol) (PVA) mat decorated with in situ grown silver nanoparticles (nano-Ag) for electrochemical glucose sensing. Ferrocene (Fc) was selected as an electron acceptor for glucose oxidase (GOD) in order to minimize the influence of oxygen. Electron transfer between GOD and Fc was facilitated by confining them within a mixed self-assembled monolayer (SAM) formed on a thin layer of gold deposited on top of the PVA/nano-Ag film. Nano-Ag was found to significantly increase the surface area of the electrode and improve the stability of electrode conductivity during tensile deformation. Electrochemical glucose detection was performed by chronoamperometry in the electroactivity domain of ferrocene, and good linearity (R2 = 0.993) was obtained in the range of 0.2-7 mM with a detection limit of 0.038 mM and a relative standard deviation (RSD) of 1.45% (n = 6). After being stuck to a bendable PDMS slice and bent, respectively, at 30° and 60° 50 times, the electrode showed slight changes in detection results (<4.78%), which remained within 8% when the bending angle increased to 90°. With its high flexibility, good detection performance, and convenient fabrication process, the proposed enzyme electrode showed good potential as a flexible platform for wearable glucose sensing systems.

Brain distribution and metabolic profiling of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats investigated by UHPLC-HRMS/MS following peripheral administration.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is known to be a tobacco-specific N-nitrosamine and has peripheral carcinogenic properties. It can also induce oxidative stress, glial cell activation, and neuronal damage in the brain. However, the distribution and metabolic characteristics of NNK in the central nervous system are still unclear. Here, a sensitive and effective UHPLC-HRMS/MS method was established to identify and investigate the metabolites of NNK and their distribution in the rat brain. In addition, the pharmacokinetic profiles were simultaneously investigated via blood-brain synchronous microdialysis. NNK and its seven metabolites were well quantified in the hippocampus, cortex, striatum, olfactory bulb, brain stem, cerebellum, and other regions of rat brain after peripheral exposure (5 mg/kg, i.p.). The average content of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in all brain regions was at least threefold higher than that of NNK, indicating a rapid carbonyl reduction of NNK in the brain. Lower concentrations of pyridine N-oxidation products in the cortex, olfactory bulb, hippocampus, and striatum might be related to the poor detoxification ability in these regions. Compared to α-methyl hydroxylation, NNK and NNAL were more inclined to the α-methylene hydroxylation pathway. Synchronous pharmacokinetic results indicated that the metabolic activity of NNK in the brain was different from that in the blood. The mean α-hydroxylation ratio in the brain and blood was 0.037 and 0.161, respectively, which indicated poor metabolic activity of NNK in the central nervous system.

Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3ß/Snail Signaling.

Background: Treating renal fibrosis is crucial to delaying chronic kidney disease. The glycogen synthase kinase-3ß (GSK-3ß)/Snail pathway regulates renal fibrosis and Renalase can ameliorate renal interstitial fibrosis. However, it is not clear whether GSK-3ß/Snail signaling affects Renalase action. Here, we explored the role and mechanism of GSK-3ß/Snail in the anti-fibrosis action of Renalase. Materials and methods: We used mice with complete unilateral ureteral obstruction (UUO) and human proximal renal tubular epithelial (HK-2) cells with transforming growth factor-ß1 (TGF-ß1)-induced fibrosis to explore the role and regulatory mechanism of the GSK-3ß/Snail pathway in the amelioration of renal fibrosis by Renalase. Results: In UUO mice and TGF-ß1-induced fibrotic HK-2 cells, the expression of p-GSK-3ß-Tyr216/p-GSK-3ß-Ser9, GSK-3ß and Snail was significantly increased, and endoplasmic reticulum (ER) stress was activated. After Renalase supplementation, fibrosis was alleviated, ER stress was inhibited and p-GSK-3ß-Tyr216/p-GSK-3ß-Ser9, GSK-3ß and Snail were significantly down-regulated. The amelioration of renal fibrosis by Renalase and its inhibitory effect on GSK-3ß/Snail were reversed by an ER stress agonist. Furthermore, when an adeno-associated virus or plasmid was used to overexpress GSK-3ß, the effect of Renalase on delaying renal fibrosis was counteracted, although ER stress markers did not change. Conclusion: Renalase prevents renal fibrosis by down-regulating GSK-3ß/Snail signaling through inhibition of ER stress. Exogenous Renalase may be an effective method of slowing or stopping chronic kidney disease progression.

Minimally invasive small incision surgical technique for unicompartmental knee arthroplasty.

PURPOSE: It is always a challenge for orthopaedic surgeons to minimise surgical incisions while ensuring excellent surgical results. We propose the minimally invasive small incision (MISI) technique and an extramedullary positioning technique in the unicompartmental knee arthroplasty (UKA) surgery. This study aimed to clarify the early postoperative clinical outcomes and component alignment between MISI and conventional minimally invasive surgical (MIS) techniques. METHODS: We prospectively enrolled 60 patients who underwent MISI-UKA and 60 patients who underwent MIS-UKA as controls. Clinical parameters include the time of straight leg raising, postoperative walking time with walker assistance, hospital stay, Numerical Rating Scale (NRS) pain score and Knee Society Score (KSS). The postoperative components and lower extremity alignment were compared between the two groups with radiographic image measurement. RESULTS: The MISI group obtained a smaller incision during knee extension (P < 0.001) but a longer tourniquet usage time than the MIS group. The MISI group lost less blood (P < 0.001). The MISI group achieved straight leg raising and walking with aid earlier after surgery, with a shorter hospital stay than the MIS group (P < 0.001). Range of motion (ROM), NRS and KSS scores revealed no significant difference between the two groups in six months postoperative follow-up (P > 0.05). Radiographic measurement results between the two groups revealed no statistical difference (P > 0.05) CONCLUSION: The MISI-UKA could achieve faster earlier recovery after surgery and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the conventional MIS-UKA.

The impact of preoperative MRI-detected lateral meniscal intra-substance signal abnormalities on mid-term functional outcomes following mobile-bearing unicompartmental knee arthroplasty.

PURPOSE: There is a dilemma as to whether the presence of degenerative changes of lateral meniscus is a contraindication to medial unicompartmental knee arthroplasty (UKA). Therefore, the purpose of this study is to assess the influence of preoperative MRI-detected lateral meniscal intra-substance signal abnormalities on mid-term functional outcomes following mobile-bearing UKA. METHODS: We performed a retrospective review of the record on a consecutive series of patients who have undergone mobile-bearing medial UKA from September 2020 to June 2023. The mean duration of follow-up was 2.34 years. All records were collected from case system. MRI assessment of lateral meniscus was performed with the use of the Stoller's classification system. Patients were categorized into two groups (grade 0 and ≥ grade 1). Patient-reported outcomes were assessed with the use of the American Knee Society functional Score (AKSS-F), American Knee Society Objective Score (AKSS-O), and Oxford Knee Score (OKS) preoperatively and at latest follow-up. Furthermore, range of motion (ROM) and hip-knee-ankle angle (HKA) were measured in preoperative and postoperative periods. RESULTS: A total of 92 patients (101 knees) were included in our study. No differences in AKSS-F, AKSS-O, OKS, HKA, or ROM were found between those who showed normal or abnormal signal change of lateral meniscus preoperatively (P < 0.05). Furthermore, there were also no significant differences between two groups concerning AKSS-F, AKSS-O, OKS, HKA, or ROM at latest postoperative follow-up (P < 0.05). Age and duration of disease were independent predictors of low postoperative AKSS-F and AKSS-O (P < 0.05). Nevertheless, ROM was an independent predictor of high postoperative AKKS-O (P < 0.05). Age and female were independent predictors of high postoperative OKS (P < 0.05). CONCLUSION: The presence of preoperative MRI-detected lateral meniscal degenerative changes did not affect mid-term functional outcomes in patients who underwent mobile-bearing medial UKA. On the basis of the results of the current study, we believe that the presence of degenerative changes of lateral meniscus is acceptable in mobile-bearing medial UKA.

Gap balance difference of unicompartmental knee arthroplasty between hanging leg and supine leg position: a prospective cohort study.

PURPOSE: Gap balance is critical in Oxford unicompartmental knee arthroplasty (OUKA) surgery; the effect of lower limb positioning on gap balance judgements has not been reported. There are two mean operative positions for OUKA patients, the hanging leg (HL) and the supine leg (SL) position. This study aimed to investigate the gap balance achieved by current UKA surgical techniques by using a force sensor, to compare the differences in gap balance between the two different positions, and to test whether the difference in gap balance leads to different outcomes in terms of component alignment and early post-operative clinical outcomes. METHODS: This prospective study included 97 knees (76 patients), who underwent OUKA from June 1, 2020, to July 31, 2021, of which 67 knees underwent UKA in the supine leg position and the other 30 in the hanging leg position. When the operator was satisfied with the gap balance, the contact forces between the trial and the spacer block were measured at 90° of knee flexion (flexion gap) and 20° of knee flexion (extension gap) using a pre-developed matrix flexible force sensor. X-rays were reviewed three to five days after surgery. Knee Society Scores (KSS) were obtained at the six month follow-up. RESULTS: Compared to the HL group, the contact force at the flexion gap was higher in the SL group: 55.15N (SD 43.36N) vs. 34.25N (SD 27.56N) (p < 0.05), whereas in the extension gap, there was no significant difference, 90.19 N (SD 43.36N) in the SL group and 86.72N (SD 43.08N) in the HL group (ns.). The contact force was greater in the extension gap than in the flexion gap in both groups (p < 0.01). The gap balance difference in the HL group was 52.46N (SD 31.33N), which was greater than that of the SL group at 35.03N (SD 19.50N) (p < 0.05). There were no significant differences in component alignment or lower limb mechanical alignment between the two groups. There was no significant difference in pre-operative and post-operative KSS between the two groups, while post-operative KSS was significantly higher in both groups compared to the pre-operative period. CONCLUSION: The intra-operative contact forces between the flexion and extension gaps differed in the two groups; the hanging leg position appeared to produce a greater difference in the judgement of gap balance than the supine leg position, but this difference did not adversely affect the alignment of the component or the early post-operative clinical outcome.

Lateral meniscus with tears or with histologic calcification does not increase the risk of lateral osteoarthritis after medial unicompartmental arthroplasty.

PURPOSE: Meniscal tears or histological meniscal calcifications (in the absence of radiological chondrocalcinosis) are frequent in osteoarthritis. Whether lateral meniscal lesions influence clinical outcomes after medial unicompartmental knee arthroplasty (UKA) is unknown. METHODS: We analyzed 130 patients (130 knees) with medial unicompartmental knee arthroplasties between 2005 and 2015. These 130 knees had full articular cartilage thickness in the lateral compartment and no radiological chondrocalcinosis on preoperative radiographs. The lateral meniscus was analyzed with preoperative MRI and a biopsy of the anterior horn at the time of surgery. Synovial fluid was collected and analyzed for calcium pyrophosphate dihydrate crystal deposition (CPPD crystals). Lateral meniscal tears were untreated when detected on MRI or during surgery, with the hypothesis that these tears on the opposite compartment would remain asymptomatic in medial UKA. At average 10-year follow-up, patients were evaluated with clinical and radiographic outcome, with a focus on the risk of joint space narrowing of the lateral femorotibial compartment. RESULTS: CPPD crystals were present in the synovial fluid of 70 knees. Lateral meniscal tears were seen on MRI in 34 (49%) normal meniscuses of the 60 knees without CPPD crystals and in six other knees without histological meniscal calcification despite CPPD crystals. Histological calcification was present on 61 lateral meniscuses with 53 meniscal tears. The results showed no significant differences in the clinical outcomes between knees with lateral meniscal tears or lateral meniscal histological chondrocalcinosis or both lesions and those without these conditions. Additionally, radiographic progression of osteoarthritis in the opposite femorotibial compartment of the knee was not more frequent in patients with these meniscal issues. The ten year cumulative survival rates, measured by the need for total knee arthroplasty, were 91% for knees without meniscal lesions and 92% for knees with these lesions. CONCLUSION: On this basis, treatment of meniscal tears of the lateral compartment and routine aspiration of the knee to assess for birefringent crystals in the planning of medial UKA do not appear necessary.

Coronal tibiofemoral subluxation under valgus stress force radiography is useful for evaluating postoperative coronal tibiofemoral subluxation in mobile-bearing UKA.

PURPOSE: Coronal tibiofemoral subluxation (CTFS) is considered a controversial and potential contraindication to unicompartmental knee arthroplasty (UKA) but is less discussed. The study aims to observe the CTFS in a cohort of patients before and after mobile-bearing UKA and to investigate the relationship between preoperative variables (preoperative CTFS and preoperative CTFS under valgus stress) and postoperative CTFS after mobile-bearing UKA. METHODS: The study retrospectively analyzed 181 patients (224 knees) undergoing mobile-bearing UKA from September 1 2019 to December 31 2021. By using hip-to-ankle anterior-posterior (AP) standing radiographs and valgus stress force radiographs, preoperative CTFS, preoperative CTFS under valgus stress, and postoperative CTFS were measured. CTFS was defined as the distance between the tangent line to the outermost joint edge of the lateral condyle of the femur and the tangent line of the lateral tibial plateau. All patients were divided into two groups based on postoperative CTFS, group A (postoperative CTFS ≤ 5 mm) and group B (postoperative CTFS > 5 mm). The Student's t-test, one-way ANOVA together with Tukey's post hoc test, the chi-square test, the Fisher's exact test, Pearson correlation analysis, simple and multiple linear regression, and univariate and multiple logistic regression were used in the analyses. RESULTS: The means ± standard deviations (SD) of preoperative CTFS, preoperative CTFS under valgus stress, and postoperative CTFS were 4.96 ± 1.82 mm, 3.06 ± 1.37 mm, and 3.19 ± 1.27 mm. The difference between preoperative CTFS and postoperative CTFS was statistically significant (p < 0.001). The preoperative CTFS (6.35 ± 1.34 mm) in Group B (n = 22) was significantly higher than that (4.81 ± 1.82 mm) in Group A (n = 202) (p < 0.001), so was the variable-preoperative CTFS under valgus stress (5.41 ± 1.00 mm (Group B) > 2.80 ± 1.14 mm (Group A), p < 0.001). In Pearson correlation analysis, there was a correlation between preoperative CTFS and postoperative CTFS (r = 0.493, p < 0.001), while the correlation between preoperative CTFS under valgus stress and postoperative CTFS was stronger (r = 0.842, p < 0.001). In multiple linear regression analysis, preoperative CTFS under valgus stress (ß = 0.798, 95% confidence interval (CI) = 0.714-0.883, p < 0.001) was significantly correlated with postoperative CTFS. In multiple logistic regression analysis, preoperative CTFS under valgus stress (OR = 12.412, 95% CI = 4.757-32.384, and p < 0.001) was expressed as the risk factor of postoperative CTFS (> 5 mm). CONCLUSION: Preoperative CTFS can be improved significantly after mobile-bearing UKA. In addition, postoperative CTFS is correlated with preoperative CTFS under valgus stress and a higher preoperative CTFS under valgus stress will increase the risk of higher postoperative CTFS (> 5 mm). LEVEL OF EVIDENCE: Level III.

Predicting valgus malalignment after mobile-bearing UKA using a new method: the arithmetic HKA of the arthritic knee.

BACKGROUND: Valgus malalignment is one of the most common reasons for the progression of osteoarthritis in the lateral compartment of the knee after mobile-bearing unicompartmental knee arthroplasty (UKA). The arithmetic hip-knee-ankle angle (aHKA) of the Coronal Plane Alignment of the Knee (CPAK) classification could reflect the constitutional alignment of the arthritic knee. The purpose of this study was to observe the relationship between the aHKA and valgus malalignment after mobile-bearing UKA. METHODS: This retrospective study was conducted using 200 knees undergoing UKA from January 1, 2019, to August 1, 2022. These radiographic signs, including preoperative hip-knee-ankle angle (HKA), mechanical proximal tibial angle (MPTA), mechanical lateral distal femoral angle (LDFA), and postoperative HKA, were measured using standardized weight-bearing long-leg radiographs. Patients with postoperative HKA > 180° and postoperative HKA ≤ 180° were classified as the valgus group and non-valgus group, respectively. The aHKA was calculated as 180° + MPTA - LDFA in this study, which had the same meaning as that (aHKA = MPTA - LDFA) in the CPAK classification. The Spearman correlation analysis, the Mann-Whitney U test, the chi-square test, the Fisher's exact test, and multiple logistic regression were used in the study. RESULTS: Of the 200 knees included in our study, 28 knees were classified as the valgus group, while 172 knees were in the non-valgus group. The mean ± standard deviation (SD) of aHKA (all groups) was 177.04 ± 2.58°. In the valgus group, 11 knees (39.3%) had a value of aHKA > 180°, while 17 knees (60.7%) had a value of aHKA ≤ 180°. In the non-valgus group, 12 knees (7.0%) had a value of aHKA > 180°, while 160 knees (93.0%) had a value of aHKA ≤ 180°. In Spearman correlation analysis, aHKA was positively correlated with postoperative HKA (r = 0.693, p < 0.001). In univariate analysis, preoperative HKA (p < 0.001), LDFA (p = 0.02), MPTA (p < 0.001), and aHKA (p < 0.001) showed significant differences between the valgus and non-valgus groups. Variables with p < 0.1 in univariate analysis were further analyzed using multiple logistic regression analysis, and the variable-aHKA (> 180° vs ≤ 180°, odds ratio (OR) = 5.899, 95% confidence interval (CI) = 1.213 to 28.686, and p = 0.028) was expressed as the risk factor of postoperative valgus malalignment. CONCLUSION: The aHKA is correlated with the postoperative alignment of mobile-bearing UKA and a high aHKA (> 180°) will increase the risk of postoperative valgus malalignment. Therefore, mobile-bearing UKA should be performed with caution in patients with preoperative aHKA > 180°.

CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/ß-catenin signaling.

OBJECTIVE: Knowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes. METHODS: The expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry. Overexpression of CYP2E1 in HCC cell was achieved by lentivirus transfection. The function of CYP2E1 were detected by CCK-8, wound healing, transwell assays, xenograft models and pulmonary metastasis model. TOP/FOPFlash reporter assay, western blotting, functional rescue experiments, Co-immunoprecipitation and reactive oxygen species detection were conducted to reveal the underlying mechanism of the tumor suppressive role of CYP2E1. RESULTS: CYP2E1 expression is down-regulated in HCC tissues, and this downregulation was associated with large tumor diameter, vascular invasion, poor differentiation, and shortened patient survival time. Ectopic expression of CYP2E1 inhibits the proliferation, invasion and migration and epithelial-to-mesenchymal transition of HCC cells in vitro, and inhibits tumor formation and lung metastasis in nude mice. Mechanistic investigations show that CYP2E1 overexpression significantly inhibited Wnt/ß-catenin signaling activity and decreased Dvl2 expression in HCC cells. An increase in Dvl2 expression restored the malignant phenotype of HCC cells. Notably, CYP2E1 promoted the ubiquitin-mediated degradation of Dvl2 by strengthening the interaction between Dvl2 and the E3 ubiquitin ligase KLHL12 in CYP2E1-stable HCC cells. CYP2E1-induced ROS accumulation was a critical upstream event in the Wnt/ß-Catenin pathway in CYP2E1-overexpressing HCC cells. CONCLUSIONS: These results provide novel insight into the role of CYP2E1 in HCC and the tumor suppressor role of CYP2E1 can be attributed to its ability to manipulate Wnt/Dvl2/ß-catenin pathway via inducing ROS accumulation, which provides a potential target for the prevention and treatment of HCC.

A radiographic model predicting the status of the anterior cruciate ligament in varus knee with osteoarthritis.

PURPOSE: The study aims to investigate the accuracy of different radiographic signs for predicting functional deficiency of anterior cruciate ligament (ACL) and test whether the prediction model constructed by integrating multiple radiographic signs can improve the predictive ability. METHODS: A total number of 122 patients from January 1, 2018, to September 1, 2021, were enrolled in this study. Among them, 96 patients were classified as the ACL-functional (ACLF) group, while 26 patients as the ACL-deficient (ACLD) group after the assessment of magnetic resonance imaging (MRI) and the Lachman's test. Radiographic measurements, including the maximum wear point of the proximal tibia% (MWPPT%), tibial spine sign (TSS), coronal tibiofemoral subluxation (CTFS), hip-knee-ankle angle (HKA), mechanical proximal tibial angle (mPTA), mechanical lateral distal femoral angle (mLDFA) and posterior tibial slope (PTS) were measured using X-rays and compared between ACLF and ACLD group using univariate analysis. Significant variables (p < 0.05) in univariate analysis were further analyzed using multiple logistic regression analysis and a logistic regression model was also constructed by multivariable regression with generalized estimating models. Receiver-operating-characteristic (ROC) curve and area under the curve (AUC) were used to determine the cut-off value and the diagnostic accuracy of radiographic measurements and the logistic regression model. RESULTS: MWPPT% (odds ratio (OR) = 1.383, 95% confidence interval (CI) = 1.193-1.603, p < 0.001), HKA (OR = 1.326, 95%CI = 1.051-1.673, p = 0.017) and PTS (OR = 1.981, 95%CI = 1.207-3.253, p = 0.007) were shown as predictive indicators of ACLD, while age, sex, side, TSS, CTFS, mPTA and mLDFA were not. A predictive model (risk score = -27.147 + [0.342*MWPPT%] + [0.282*HKA] + [0.684*PTS]) of ACLD using the three significant imaging indicators was constructed through multiple logistic regression analysis. The cut-off values of MWPPT%, HKA, PTS and the predictive model were 52.4% (sensitivity:92.3%; specificity:83.3%), 8.5° (sensitivity: 61.5%; specificity: 77.1%), 9.6° (sensitivity: 69.2%; specificity: 78.2%) and 0.1 (sensitivity: 96.2%; specificity: 79.2%) with the AUC (95%CI) values of 0.906 (0.829-0.983), 0.703 (0.574-0.832), 0.740 (0.621-0.860) and 0.949 (0.912-0.986) in the ROC curve. CONCLUSION: MWPPT% (> 52.4%), PTS (> 9.6°), and HKA (> 8.5°) were found to be predictive factors for ACLD, and MWPPT% had the highest sensitivity of the three factors. Therefore, MWPPT% can be used as a screening tool, while the model can be used as a diagnostic tool.

Bioactive peptide apelin rescues acute kidney injury by protecting the function of renal tubular mitochondria.

Mitochondrial dysfunction in proximal tubular epithelial cells is a key event in acute kidney injury (AKI), which is a risk factor for the development of chronic kidney disease (CKD). Apelin is a bioactive peptide that protects against AKI by alleviating inflammation, inhibiting apoptosis, and preventing lipid oxidation, but its role in protecting against mitochondrial damage remains unknown. Herein, we examined the protective effects of apelin on mitochondria in cisplatin-stimulated human renal proximal tubular epithelial cells and evaluated its therapeutic efficacy in cisplatin-induced AKI mice. In vitro, apelin inhibited the cisplatin-induced mitochondrial fission factor (MFF) upregulation and the fusion-promoting protein optic atrophy 1 (OPA1) downregulation. Apelin co-treatment reversed the decreased levels of the deacetylase, Sirt3, and the increased levels of protein acetylation in mitochondria of cisplatin-stimulated cells. Overall, apelin improved the mitochondrial morphology and membrane potential in vitro. In the AKI model, apelin administration significantly attenuated mitochondrial damage, as evidenced by longer mitochondrial profiles and increased ATP levels in the renal cortex. Suppression of MFF expression, and maintenance of Sirt3 and OPA1 expression in apelin-treated AKI mice was also observed. Finally, exogenous administration of apelin normalized the serum level of creatinine and urea nitrogen and the urine levels of NGAL and Kim-1. We also confirmed a regulatory pathway that drives mitochondrial homeostasis including PGC-1α, ERRα and Sirt3. In conclusion, we demonstrated that apelin ameliorates renal functions by protecting tubular mitochondria through Sirt3 upregulation, which is a novel protective mechanism of apelin in AKI. These results suggest that apelin has potential renoprotective effects and may be an effective agent for AKI treatment to significantly retard CKD progression.

Anthropometry of the medial femoral condyle in the Chinese population: the morphometric analysis to design unicomparmental knee component.

BACKGROUND: This study aimed to assess the radii of the distal and posterior articular surfaces of the medial femoral condyle in a Chinese population and provide detailed parameters of the knee joint for the future design of UKA components. METHODS: This study included 500 consecutive Chinese patients who underwent knee MRI from Jan 2019 to Jan 2020. The two most appropriate circles were used to reveal the distal and posterior joint surfaces in the sagittal plane of the MRI images. The radius of the circle representing the distal articular surface in the sagittal plane was measured as R1, and the radius of the posterior articular surface was measured as R2. The distance between the centers of the two rotation circles was recorded as d. An independent t test was used to compare the differences between men and women. The Pearson correlation coefficient was calculated to analyze the correlation between R1 and R2. SPSS v19.0 software was used for statistical analysis. RESULTS: The average values of R1, R2, R1/R2 and d were calculated. Scatter plots were constructed to show the trend of changes in the radius of the distal and posterior articular surfaces of the femoral condyle. R1, R2 and d differed significantly between men and women (p < 0.05). Correlation analysis showed that R1 was positively correlated with R2 (r = 0.61, p < 0.05). CONCLUSIONS: The data of the radii of the distal and posterior articular surfaces of the medial femoral condyle were provided. In the UKA design, the relationships between the radii of the distal and posterior articular surfaces should be taken into account.

There are isoheight points that measure constant femoral condyle heights along the knee flexion path.

PURPOSE: It is a challenge to evaluate the maintenance of medial and lateral soft tissue balance in total knee arthroplasty (TKA). This study aimed to determine the "isoheight" points and the "isoheight" axis (IHA) that can measure constant medial/lateral condyle heights during flexion of the knee, and compare the IHA with two major anatomical axes, the transepicondylar axis (TEA) and the geometric center axis (GCA). METHODS: Twenty-two healthy human knees were imaged using a combined MRI and dual fluoroscopic imaging system while performing a single-legged lunge (0°-120°). The isoheight points of the medial and lateral femoral condyles were defined as the locations with the least amount of changes in heights during the knee flexion; an IHA is the line connecting the medial and lateral isoheight points. The measured changes of the condyle heights using the IHA were compared with those measured using the TEA and GCA. RESULTS: Overall, the IHA was posterior and distal to the TEA, and anterior to the GCA. The isoheight points measured condyle height changes within 1.2 ± 2.3 mm at the medial and 0.7 ± 3.3 mm at the lateral sides during the knee flexion. Between 0° and 45°, the condyle height changes measured using the GCA (medial: 3.0 ± 1.8 mm, lateral: 2.3 ± 2.0 mm) were significantly larger than those of the IHA and the TEA (p < 0.05). Between 90° and 120°, the changes of the condyle heights measured using the TEA (medial: 5.3 ± 1.8 mm, lateral: 3.3 ± 1.8 mm) were significantly larger than those of the IHA and GCA (p < 0.05). CONCLUSION: There are isoheight points in the medial and lateral femoral condyles that can measure constant heights along the full range of knee flexion and could be used to formulate an "isoheight" axis (IHA) of the femur. The condyle height changes measured by the TEA and GCA were greater than the IHA measurements along the flexion path. These data could be used as a valuable reference to evaluate the condyle height changes after TKA surgeries and help achieve soft tissue balance and optimal knee kinematics along the flexion path. LEVEL OF EVIDENCE: IV.

Patient-specific instrumentation (PSI) in total ankle arthroplasty: a systematic review.

BACKGROUND: Patient-specific instrument (PSI) may theoretically make total ankle arthroplasty (TAA) more accurate. Several studies have reported the outcomes of PSI TAA. The aim of this study is to systematically review the literature of PSI TAA. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for PSI TAA. The quality of the included studies was evaluated according to Methodological Index for Non-Randomized Studies (MINORS). RESULT: Nine articles were ultimately included in the systematic review. The implant position and function outcome of TAA was similar between PSI and SI. Prediction accuracy of implant size remained great difference. PSI can shorten the operative time and fluoroscopy time. The quality of current studies on PSI TAA is insufficient to produce high-level evidence. CONCLUSION: PSI can get similar implant position and clinical outcome in TAA compared to SI, but current evidence is not strong enough to evaluate PSI TAA.

Cannulated screw fixation versus plate fixation in treating displaced intra-articular calcaneus fractures: a systematic review and meta-analysis.

BACKGROUND: Operative treatment has become the current trend for displaced intra-articular calcaneus fracture (DIACF), while using cannulated screw fixation or plate fixation is still controversial for treating DIACF. The purpose of this meta-analysis is to compare the outcome of the two fixation methods. METHODS: We searched literature comparing cannulated screw fixation and plate fixation from PubMed, Embase, Web of Science, and Cochrane Library. Only randomized controlled trials were included. The outcomes of post-operative function, radiological measurement, time efficiency, and wound complications were pooled in the meta-analysis. RESULT: Seven RCTs with 902 cases of DIACF were included. Pooled results showed the two fixation methods that had similar function satisfactory of AOFAS score (RR = 0.95, 95% CI = [0.83, 1.09], P = 0.47, I2 = 0%) and Maryland Foot score (RR = 0.93, 95% CI = [0.68, 1.28], P = 0.66, I2 = 84%). Compared to plate fixation, cannulated screw fixation had better improvement of Bohler's angle (WMD = 0.56, 95% CI = [0.20, 0.91], P = 0.002, I2 = 34%) and Gissane's angle (WMD = 1.36, 95% CI = [0.56, 2.16], P = 0.0008, I2 = 7%), better recovery of calcaneal height (WMD = 0.49, 95% CI = [0.02, 0.95], P = 0.04, I2 = 6%), shorter time to operation (WMD = - 2.91, 95% CI = [- 4.99, - 0.84], P = 0.006, I2 = 97%), less operation time (WMD = - 21.58, 95% CI = [- 37.31, - 5.85], P = 0.007, I2 = 98%), reduced length of hospital stay (WMD = - 2.00, 95% CI = [- 3.69, - 0.31], P = 0.02, I2 = 97%), and less wound complications (RR = 0.16, 95% CI = [0.08, 0.32], P < 0.00001, I2 = 0%). CONCLUSION: Cannulated screw fixation and plate fixation have similar postoperative functional satisfactory. Cannulated screw fixation is superior to plate fixation in reduction quality, time efficiency, and wound complications.

Sensor and machine learning-based assessment of gap balancing in cadaveric unicompartmental knee arthroplasty surgical training.

PURPOSE: The aim of this study was to assess the difference between flexion and extension contact forces-gap balance-after Oxford mobile-bearing medial unicompartmental knee arthroplasty (UKA) performed by surgeons with varying levels of experience. METHODS: Surgeons in a training programme performed UKAs on fresh frozen cadaveric specimens (n = 60). Contact force in the medial compartment of the knee was measured after UKA during extension and flexion using a force sensor, and values were clustered using an unsupervised machine learning (k-means algorithm). Univariate analysis was performed with general linear regression models to identify the explanatory variable. RESULTS: The level of experience was predictive of gap balance; surgeons were clustered into beginner, mid-level and experienced groups. Experienced surgeons' mean difference between flexion and extension contact force was 83 N, which was significantly lower (p < 0.05) than that achieved by mid-level (215 N) or beginner (346 N) surgeons. CONCLUSION: We found that the lowest mean difference between flexion and extension contact force after UKA was 83 N, which was achieved by surgeons with the most experience; this value can be considered the optimal value. Beginner and mid-level surgeons achieved values that were significantly lower. This study also demonstrates that machine learning can be used in combination with sensor technology for improving gap balancing judgement in UKA.

Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Reducing tourniquet inflation time is important because of the complications of tourniquet extensively used for the control of hemorrhage in total knee arthroplasty (TKA). Bleeding management is critical to acquire a relative bloodless arthrotomy interface for maximize cement fixation in non-tourniquet TKA. The purpose of this study was to investigate hemostatic and hemodynamic effects of epinephrine-soaked gauzes in cemented TKAs. METHODS: A retrospective cohort study of 101 patients in two groups was performed. The first group (n = 51) underwent unilateral TKA with our procedures of epinephrine use, the second group (n = 50) had the same protocol with tourniquet and no epinephrine utilization. Surgical field visualization was assessed by grading scale for difficulty of intraoperative visualization due to blood and number of surgical field clearances. Perioperative blood loss was recorded. Hemodynamic parameters were observed in the epinephrine group. RESULTS: There was statistically significant difference (p < 0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant difference (p = 0.96) between two groups before cementing. No statistically significant result on numbers of surgical field clearances between two groups (p = 0.25) was found. Epinephrine group showed significant difference in hidden blood loss compared with no epinephrine group (576.6 ± 229.3 vs 693.2 ± 302.9, respectively, p = 0.04). The hemodynamic effects of epinephrine may be under control. CONCLUSION: The procedure of epinephrine soaked gauzes, as a prudent adjunct, may be effective to reduce blood loss and obtain bloodless bone sections in non-tourniquet TKAs, regardless of hemodynamics.