Identification of the inhibition mechanism of carbonic anhydrase II by fructooligosaccharides.

Polygonatum sibiricum (P. sibiricum), recognized as a precious nourishing Chinese traditional medicine, exhibits the pharmacological effect of anti-aging. In this work, we proposed a novel mechanism underlying this effect related to the less studied bioactive compounds fructooligosaccharides in P. sibiricum (PFOS) to identify the inhibition effect of the small glycosyl molecules on the age-related zinc metalloprotease carbonic anhydrase II (CA II). Molecular docking and molecular dynamics simulation were used to investigate the structural and energetic properties of the complex systems consisting of the CA II enzyme and two possible structures of PFOS molecules (PFOS-A and PFOS-B). The binding affinity of PFOS-A (-7.27 ± 1.02 kcal/mol) and PFOS-B (-8.09 ± 1.75 kcal/mol) shows the spontaneity of the binding process and the stability of the combination in the solvent. Based on the residue energy decomposition and nonbonded interactions analysis, the C-, D- and G-sheet fragments of the CA II were found to be crucial in binding process. Van der Waals interactions form on the hydrophobic surface of CAII mainly with 131PHE and 135VAL, while hydrogen bonds form on the hydrophilic surface mainly with 67ASN and 92GLN. The binding of PFOS results in the blocking of the zinc ions pocket and then inhibiting its catalytic activity, the stability of which has been further demonstrated by free energy landscape. These findings provide evidence of the effective inhibition of PFOS to CA II enzyme, which leads to a novel direction for exploring the mechanism of traditional Chinese medicine focused on small molecule fructooligosaccharides.

Low expression of ELOVL6 may be involved in fat loss in white adipose tissue of cancer-associated cachexia.

BACKGROUND: Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat plays an important role. The mechanisms of CAC-induced fat loss include the enhancement of lipolysis, inhibition of lipogenesis, and browning of white adipose tissue (WAT). However, few lipid-metabolic enzymes have been reported to be involved in CAC. This study hypothesized that ELOVL6, a critical enzyme for the elongation of fatty acids, may be involved in fat loss in CAC. METHODS: Transcriptome sequencing technology was used to identify CAC-related genes in the WAT of a CAC rodent model. Then, the expression level of ELOVL6 and the fatty acid composition were analyzed in a large clinical sample. Elovl6 was knocked down by siRNA in 3T3-L1 mouse preadipocytes to compare with wild-type 3T3-L1 cells treated with tumor cell conditioned medium. RESULTS: In the WAT of patients with CAC, a significant decrease in the expression of ELOVL6 was found, which was linearly correlated with the extent of body mass reduction. Gas chromatographic analysis revealed an increase in palmitic acid (C16:0) and a decrease in linoleic acid (C18:2n-6) in these tissue samples. After treatment with tumor cell-conditioned medium, 3T3-L1 mouse preadipocytes showed a decrease in Elovl6 expression, and Elovl6-knockdown cells exhibited a reduction in preadipocyte differentiation and lipogenesis. Similarly, the knockdown of Elovl6 in 3T3-L1 cells resulted in a significant increase in palmitic acid (C16:0) and a marked decrease in oleic acid (C18:1n-9) content. CONCLUSION: Overall, the expression of ELOVL6 was decreased in the WAT of CAC patients. Decreased expression of ELOVL6 might induce fat loss in CAC patients by potentially altering the fatty acid composition of adipocytes. These findings suggest that ELOVL6 may be used as a valuable biomarker for the early diagnosis of CAC and may hold promise as a target for future therapies.

Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing.

BACKGROUND: From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN: Retrospective study. PURPOSE: To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS: 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS: There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS: The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.

Construction of self-enhanced luminescence probes based on Ti3C2 reducibility for ultrasensitive PNK analysis.

Au nano-clusters (Au NCs) were promising electrochemiluminescence (ECL) nano-materials. However, the small size of Au NCs presented a challenge in terms of their immobilization during the construction of an ECL biosensing platform. This limitation significantly hindered the wider application of Au NCs in the ECL field. In this work, we successfully used the reducibility of Ti3C2 to fabricate in situ a self-enhanced nano-probe Ti3C2-TiO2-Au NCs. The strategy of in situ generation not only improved the immobilization of Au NCs on the probe but also eliminated the requirement of adding reducing agents during preparation. In addition, in situ generated TiO2 could serve as a co-reaction accelerator, shortening the electron transfer distance between S2O82- and Au NCs, thereby improving the utilization of intermediates and enhancing the ECL response of Au NCs. The constructed ECL sensing platform could achieve sensitive detection of polynucleotide kinase (PNK). At the same time, the 5'-end phosphate group of DNA phosphorylation could chelate with a large amount of Ti on the surface of Ti3C2, thereby achieving the goal of specific detection of PNK. The sensor based on self-enhanced ECL probes had a broad dynamic range spanning for PNK detection from 10.0 to 1.0 × 107 µU mL-1, with a limit of detection of 1.6 µU mL-1. Moreover, the ECL sensor showed satisfactory detection performance in HeLa cell lysate and serum. This study not only provided insights for addressing the issue of ECL luminescence efficiency in Au NCs but also presented novel concepts for ECL self-enhancement strategies.

Highly sensitive fiber-optic chemical pH sensor based on surface modification of optical fiber with ZnCdSe/ZnS quantum dots.

The pH value plays a vital role in many biological and chemical reactions. In this work, the fiber-optic chemical pH sensors were fabricated based on carboxyl ZnCdSe/ZnS quantum dots (QDs) and tapered optical fiber. The photoluminescence (PL) intensity of QDs is pH-dependence because protonation and deprotonation can affect the process of electron-hole recombination. The evanescent wave of tapered optical fiber was used as excitation source in the process of PL. To obtain higher sensitivity, the end faces of fiber were optimized for cone region. By lengthening the cone region and shrinking the end diameter of optical fiber, evanescent wave was enhanced and the excitation times of QDs were increased, which improved the PL intensity and the sensitivity of the sensor. The sensitivity of sensor can reach as high as 0.139/pH in the range of pH 6.00-9.01. The surface functional modification was adopted to prepare sensing films. The carboxyl groups on the QDs ligands are chemically bonded to the fiber surface, which is good for response time (40 s) and stability (decreased 0.9 % for 5 min). These results demonstrated that ZnCdSe/ZnS QDs-based fiber-optic chemical pH sensors are promising approach in rapid and precise pH detection.

Sound Touch Elastography for Noninvasive Assessment of Liver Stiffness in Patients With Chronic Heart Failure.

Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction ≤40%, n = 45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n = 40), and right-sided HF (RHF) groups (n = 25); normal groups (n = 40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 ± 1.1 kPa in normal subjects and increased slightly to 5.9 ± 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 ± 2.0 kPa and 10.3 ± 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens.

Comparison of Clinical Outcomes Between Modern Augmented ACL Repair and Autograft ACL Reconstruction: A Systematic Review and Meta-analysis of Studies With Minimum 2-Year Follow-up.

Background: Anterior cruciate ligament (ACL) reconstruction has been the gold standard for primary ACL rupture since the 1990s. In the past decade, ACL repair has received renewed attention and increased research. Purpose: To compare the clinical outcomes of modern augmented ACL repair versus autograft reconstruction for ACL ruptures. Study Design: Systematic review; Level of evidence, 3. Methods: A search of the PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases was conducted for prospective or retrospective comparative studies published between January 1, 2010, and January 3, 2023, with a minimum 2-year follow-up. Two independent reviewers performed data extraction and methodological quality assessment. Sensitivity analysis was performed to maintain the stability of results. Results: Nine studies were included (minimum follow-up period, 24-60 months). The total sample size was 833 patients (augmented repair group: 358 patients; autograft ACL reconstruction group: 475 patients). There were 4 randomized controlled trials (level 1), 1 prospective comparative study (level 2), 2 retrospective comparative studies (level 3), and 2 case-control studies (level 3). The augmented ACL repair group attained significantly higher Lysholm score (weighted mean difference [WMD] = 1.57; 95% confidence interval [CI], 0.14-3.01; P = .03) and hamstring strength (WMD = 36.69; 95% CI, 29.07-44.31; P < .01) but had higher rates of hardware removal (odds ratio [OR] = 6.30; 95% CI, 2.44-16.23; P = .0001), reoperation (OR = 1.87; 95% CI, 1.33-2.62; P = .0003), and failure (OR = 1.58; 95% CI, 1.03-2.43; P = .0003) compared with the autograft ACL reconstruction group. No significant differences were observed between the repair and reconstruction groups regarding postoperative International Knee Documentation Committee scores, Tegner scores, knee laxity, satisfaction, ACL revisions, complications, and reoperation rather than revision. Conclusion: Augmented ACL repair was associated with higher rates of reoperation, hardware removal, and failure compared with autograft ACL reconstruction in studies with minimum 2-year follow-up data. However, augmented ACL repair had higher Lysholm scores and hamstring strength versus autograft ACL reconstruction.

Epidemiology of Lateral Patellar Dislocation Including Bone Bruise Incidence: Five Years of Data from a Trauma Center.

OBJECTIVE: Systematic summary of the epidemiology of patellar dislocation is rare. This study aims to investigate sex-, age-, type-, injury causing events-, incidence of bone bruise and time from last injury (TFLI)-specific characteristics, and detail the epidemiological characteristics of patellar dislocation. METHOD: In this descriptive epidemiological study, a total of 743 patients who have a history of lateral patellar dislocation with either first-time patellar dislocation (FPD) or recurrent patellar dislocation (RPD) between August 2017 and June 2022 at our institution met the inclusion criteria and were selected in this study. Patient characteristics including the type, gender, age, events leading to patellar dislocation, incidence of patellar bone bruise, and the time from last injury (TFLI) of patellar dislocation were retrospectively obtained and described. Magnetic resonance imaging scans (MRI) of the knee were reviewed for insuring bone bruise. RESULTS: Among the 743 patients with patellar dislocation who required surgical reconstruction of the medial retinaculum, 418 (56.2%) had RPD and 325 (43.8%) had FPD. There were more females (65.0%) than males (35.0%) in patellar dislocation patients. Among the female patients, those aged <18 years had higher incidence (31.4%) of patellar dislocation. Among the male patients, those aged <18 and 19-28 years had higher incidence (16.8%) of patellar dislocation. Of all age groups, the prevalence rate of patellar dislocation was high in juvenile population and females, but with no statistical significance. The most common patellar dislocation-causing event was sport accidents (40.1%), followed by life accidents (23.2%). The incidence of left-knee patellar dislocation was slightly higher than that of right-knee patellar dislocation. The incidence of patellar bone bruise of RPD (63.2%) was significantly lower (p < 0.05) than that of FPD (82.2%). Patellar dislocation patients with bone bruise had shorter time from last injury (TFLI) than those without patellar bone bruise (p < 0.05). CONCLUSIONS: The incidence of bone bruise of RPD was lower than that of FPD, and patients with patellar bone bruise may have a shorter time from last injury than those without bone bruise.

An electrochemiluminescence aptasensor based on Ti3C2 QDs-1T/2H MoS2 nano-hybrid material for the highly sensitive detection of lincomycin.

Developing a highly selective and sensitive analysis strategy for lincomycin (LIN) is of great significance for environmental protection and food safety. Herein, we reported a novel electrochemiluminescence (ECL) aptasensor based on Ti3C2 QDs-1T/2H MoS2 nano-hybrid luminophore for detection of LIN. The hybridization of Ti3C2 QDs and 1T/2H MoS2 endowed nanocomposite with structural and compositional advantages for boosting the ECL performance of QDs by about three times. This enhancement could be attributed to the remarkable electrocatalytic activity and high conductivity exhibited by 1T/2H MoS2. Secondly, the great surface area of 1T/2H MoS2 is conducive to the high dispersion of Ti3C2 QDs, and its good conductivity could promote charge transfer. On the other hand, the excellent catalytic performance of 1T/2H MoS2 could facilitate the reduction of S2O82- to produce more radical, which significantly enhance the ECL signal of Ti3C2 QDs. Given these features, a sensor for detection of LIN was established based on specific recognition between target and aptamer. The sensor showed a good linear relationship (0.05 ng mL-1 ∼100 µg mL-1) with a detection limit as low as 0.02 ng mL-1. It is worth noting that this work has been validated in testing milk samples, exhibiting great potential application prospects in food analysis.

Clinical influencing factors affecting pulmonary hypertension in hemodialysis patients

Background: The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. Methods: This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. Results: The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6-2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3-4.6 L) and 1.4 L (range, 0.6-2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570-1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7-982.2 mL/min) and 790 mL/min (range, 591-1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08-1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09-1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01-1.28; p = 0.03) were risk factors. Conclusion: Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients.

Effects of different roasting temperatures on rabbit meat protein oxidation and fluorescent carbon nanoparticle formation.

This study explores the oxidation of rabbit meat proteins and the physicochemical properties of the resulting fluorescent carbon nanoparticles (CNPs) under various roasting temperatures (180, 210, 240, 270, and 300 °C). The determination of sulfhydryl content, along with the results from UV and fluorescence spectroscopy, indicates that the protein structure undergoes changes during the roasting process, and the degree of oxidation shows an increasing trend with rising roasting temperatures. The CNP solution obtained exhibits a typical blue fluorescence. Moreover, as the roasting temperature increases from 180 °C to 300 °C, the relative content of the three elements in CNPs, namely C, N, and O, increases by 12 %, -3%, and -9 %, respectively. The surface of the obtained rabbit meat CNPs contains hydrophilic and polycyclic groups, such as carbonyl, hydroxyl, and amide bonds. Correlation analysis reveals a significant positive correlation between the degree of protein oxidation and the fluorescence intensities of CNPs.

Comparison of Bone Bruise Pattern Epidemiology between Anterior Cruciate Ligament Rupture and Patellar Dislocation Patients-Implications of Injury Mechanism.

Different bone bruise patterns observed using magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different knee injury mechanisms. In this study, 77 ACL ruptures and 77 patellar dislocations in knee MR images taken from patients with bone bruises at our institution between August 2020 and March 2022 were selected and analyzed. In order to determine typical bone bruising patterns following by ACL rupture and patellar dislocation, sagittal- and transverse-plane images were used to determine bone bruise locations in the directions of medial-lateral and superior-inferior with MR images. The presence, intensity, and location of the bone bruises in specific areas of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns after ACL rupture and patellar dislocation were classified. The results showed that there were four kinds of bone bruise patterns (1-, 2-, 3-, and 4- bone bruises) after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including the lateral femoral condyle and both the lateral-medial tibial plateau, LF + BT; both the lateral-medial femoral condyle and the lateral tibial plateau, BF + LT; and the medial femoral condyle and both the medial and lateral tibial plateau, MF + BT) followed by 4- bone bruises (both the lateral-medial femoral condyle and the tibial plateau, BF + BT), 2- bone bruises (the lateral femoral condyle and tibial plateau, LF + LT; the medial femoral condyle and the lateral tibial plateau, MF + LT; the lateral femoral condyle and the medial tibial plateau, LF + MT; the medial femoral condyle and the tibial plateau, MF + MT; both the lateral-medial tibial plateau, 0 + BT), and 1- bone bruise (only the lateral tibial plateau, 0 + LT). There was only a 1- bone bruise (the latera femoral condyle and medial patella bone bruise) for patellar dislocation, and the most common pattern of patellar dislocation was in the inferior medial patella and the lateral anterior inferior femur. The results suggested that bone bruise patterns after ACL rupture and patellar dislocation are completely different. There were four kinds of bone bruise patterns after non-contact ACL rupture, while there was only one kind of bone bruise pattern after patellar dislocation in patients, which was in the inferior medial patella and lateral anterior inferior femur.

The apex of the deep cartilage is a stable landmark to position the femoral tunnel during remnant-preserving anterior cruciate ligament reconstruction.

PURPOSE: The aim of this retrospective cohort study was to investigate whether the apex of the deep cartilage (ADC) could help surgeons position the femoral tunnel accurately in remnant-preserving anterior cruciate ligament (ACL) reconstruction (ACLR). METHODS: In the current retrospective cohort study, a total of 134 patients who underwent ACLR between 2016 and 2020 were included. The femoral tunnel position was located using ADC as the landmark. The patients were divided into two groups: the remnant-preserving group (RP group, n = 68) underwent remnant-preserving ACLR, and the nonremnant group (NRP group, n = 66) underwent traditional ACLR with remnant removal. Postoperatively, the femoral tunnel position was evaluated on 3D-CT. The length from the ADC to the shallow cartilage margin (L) and to the centre of the femoral tunnel (l) and the length from the centre of the femoral tunnel to a low cartilage ratio in the direction from high to low (H) were measured. RESULTS: The l/L values of the RP and NRP groups were both 0.4 ± 0.1 after rounding (n.s.), and the H values were 9.3 ± 1.6 mm and 9.3 ± 1.7 mm, respectively (n.s.). There was no significant difference in l/L or H between the two groups. The estimation plot also showed high consistency of H and l/L of the two groups. The inter- and intraobserver reliability of I, L, l/L, and H were almost perfect. CONCLUSIONS: The apex of the deep cartilage is a good landmark for positioning the femoral tunnel in remnant-preserving ACL reconstruction. LEVEL OF EVIDENCE: Level III.

There is no difference in the efficacy of anterior cruciate ligament reconstruction using autograft combined with or without ligament augmentation: a systematic review and meta-analysis.

PURPOSE: This study aims to determine the efficacy of anterior cruciate ligament reconstruction (ACLR) using autograft combined with or without ligament augmentation. METHODS: A computerized search of the databases was conducted, including PubMed, Web of Science, Embase, Scopus and the Cochrane Library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for the pooling of results. Sensitivity analysis was performed to maintain the stability of results. The egger test was applied to assess the publication bias. RESULTS: Fourteen studies were included. The total cohort was 1353 patients (non-augmented group: 763 patients; augmented group: 590 patients). There were three Randomized Controlled Trials (RCTs, Level I), six retrospective comparative studies (Level III) and five case-control studies (Level III). The follow-up rate was ≥ 88% and the follow-up periods were ≥ 24 months in all included studies. The augmented graft used to compare with autograft included the Ligament Augmentation Device (LAD), the Ligament Advanced Reinforcement System (LARS) artificial ligament, FiberTape, hamstring tendon allograft, degradable poly (urethane urea). No significant differences were observed between the augmented and non-augmented groups regarding postoperative patient-reported outcomes (PROs), including the International Knee Documentation Committee score, Lysholm score and Tegner score, knee laxity, including KT-1000, side-to-side difference, Lachman test and pivot shift and rate of graft failure. CONCLUSIONS: ACLR using autografts combined with ligament augmentation shows no advantages in PROs, knee laxity and graft failure rate compared with using autografts only. LEVEL OF EVIDENCE: Level III. TRIAL REGISTRATION: The research protocol was registered at the PROSPERO database (CRD42022324784).

The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization.

OBJECTIVE: Cachexia, marked by muscle atrophy, poses substantial challenges for prevention and treatment. This study delves into the unclear role of butyrate, a gut microbiota metabolite, in cachexia by examining gut microbiota and short-chain fatty acid (SCFA) profiles in human and mouse fecal samples. METHODS: We analyzed cachexia-associated gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomic techniques. Mouse cachexia models were developed with C26 cells, and LPS was used to induce muscle cell atrophy in C2C12 cells. We evaluated butyrate's in vivo effects on intestinal health, muscle preservation, inflammation, and macrophage activity. In vitro studies focused on butyrate's influence on macrophage polarization and the subsequent effects on muscle cells. RESULTS: Both cachexia patients and mice exhibited gut microbiota imbalances, irregular butyrate concentrations, and a decline in butyrate-producing bacteria. In vivo tests showed that butyrate counteract cachexia-induced muscle atrophy by adjusting the Akt/mTOR/Foxo3a and Fbox32/Trim63 pathways. These butyrate also bolstered intestinal barrier integrity, minimized endotoxin migration, and mitigated oxidative stress. Furthermore, butyrate curtailed inflammation and macrophage penetration in muscles. In vitro experimental results demonstrate that butyrate inhibit macrophage polarization towards the M1 phenotype and promote polarization towards the M2 phenotype. Both M1 and M2 macrophages influence the aforementioned pathways and oxidative stress, participating in the regulation of muscle cell atrophy. CONCLUSION: Our study delineates the intricate interplay between gut microbiota dysbiosis, butyrate fluctuations, and cachexia progression. Butyrate not only reinforces the intestinal barrier but also orchestrates macrophage polarization, mitigating muscle atrophy and averting cachexia-induced muscle deterioration. Concurrently, the M1 and M2 macrophages play pivotal roles in modulating skeletal muscle cell atrophy. This highlights the potential of utilizing the gut-derived metabolite butyrate as a promising therapeutic approach for addressing cachexia-related issues.

Increased Lateral Femoral Condyle Ratio Measured by Magnetic Resonance Imaging Is Associated With Anterior Cruciate Ligament Rerupture.

PURPOSE: To investigate the association between lateral femoral condyle ratio (LFCR) measured by magnetic resonance imaging (MRI) and anterior cruciate ligament (ACL) rerupture after anatomic ACL reconstruction (ACLR) and to compare the diagnostic accuracy between MRI and radiograph measurements. METHODS: A retrospective review was conducted on patients who underwent anatomic ACLR in our institution between 2015 and 2018. Patients who experienced rerupture after ACLR were identified and matched 1:1 with control patients who showed no evidence of graft failure during a minimum 48-month follow-up. The matching criteria included age, sex, and body mass index. LFCR was measured on MRI scans and radiographs of the affected limb. Patients' characteristics, surgical features, and anatomic measurements were compared between groups. Conditional logistic regression was performed to investigate whether MRI-measured LFCR is a risk factor for ACL rerupture. The optimal cutoff value was determined by receiver operating characteristic curves (ROC). Delong's test was performed to compare the diagnostic accuracy between MRI and radiograph measurements. RESULTS: A total of 72 patients who sustained ACL rerupture were included and matched with 72 control subjects. Compared to patients with intact ACLR, those who sustained ACL rerupture showed a significant increase in LFCR on MRI scans (63.38% ± 2.26% [95% CI, 62.84%-63.91%] vs 61.10% ± 2.19% [95% CI, 60.59%-61.61%], P < .001). An MRI-measured LFCR >62.18% was set as the cutoff point to discern patients at a higher risk of graft failure after anatomic ACLR, with sensitivity and specificity of 75.0% and 70.8%, respectively. MRI-measured LFCR demonstrated superior diagnostic accuracy during ROC curve analysis, achieving a higher area under the curve compared to radiograph-measured LFCR (0.783 ± 0.051 vs 0.668 ± 0.060, P = .041). CONCLUSIONS: The study found that MRI-measured LFCR was associated with ACL rerupture. A cutoff value of 62.18% was determined, which can help identify patients at a higher risk of rerupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction.

BACKGROUND: The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR. METHODS: A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS). RESULTS: No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group. CONCLUSION: Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group. Level of evidence Level III.

Using a Xenogeneic Acellular Dermal Matrix Membrane to Enhance the Reparability of Bone Marrow Mesenchymal Stem Cells for Cartilage Injury.

Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models.

Effects of recipient education disparity on living donor kidney transplant outcomes across different ethnic groups: a retrospective study in the United States.

Background: Previous studies have shown that education level is associated with the prognosis of cadaveric kidney transplant recipients. However, it is unclear whether education affects the prognosis of living kidney transplant (LDKT) recipients. In addition, it remains to be determined whether the uneven distribution of educational levels consistently affects the prognosis of LDKT recipients across ethnic groups (White, Black, Hispanic and Asian). Methods: After establishing inclusion and exclusion criteria, we conducted a retrospective study of LDKT recipients who received their first single LDKT between 2005 and 2020. The LDKT recipients were divided into lower- and higher-education groups according to categorize the educational level of recipients, and transplant outcomes, including graft survival, patient survival, and death-censored graft survival (DCGS), were analyzed and compared. Results: Graft survival, DCGS and patient mortality were significantly better in the higher-education group compared with those in the lower-education group (P<0.001), with the risk of graft failure, death censored graft failure (DCGF) and patient mortality increasing by 11%, 15% and 7% in the lower-education group, respectively. Furthermore, compared with the higher-education group, the risk of graft failure in Black recipients increased by 18% [adjusted hazard ratio (aHR), 1.18; 95% confidence interval (CI): 1.07 to 1.30], and the risk of patient mortality among White recipients decreased by 7% (aHR, 0.93; 95% CI: 0.87 to 0.99). However, there were no significant differences in graft failure and patient mortality among Hispanic and Asian recipients, respectively. Conclusions: This study revealed that LDKT recipients with a higher education level had better transplant outcomes. However, these transplant outcome differences were mainly found in White and Black recipients. These data confirm the significant effect of different levels of education on the prognosis of LDKT recipients.

Development and application of the Cancer Cachexia Staging Index for the diagnosis and staging of cancer cachexia.

OBJECTIVE: The current tools for evaluating cancer cachexia are either too simple to reflect the far-reaching effects of cachexia or too complicated to be used in daily practice. This study aimed to develop a cancer cachexia staging index (CCSI) that is both practical and comprehensive. METHODS: Patients with gastrointestinal cancers were prospectively included in the study. Clinical data including weight change, body composition, systematic inflammation, nutrition, and function status were entered into regression models to determine the best variable combination as well as their respective cutoff values and score distribution in the CCSI. The CCSI's ability to predict outcomes and evaluate the consequences of cachexia for patients were then assessed. RESULTS: Clinical information and test results from 10 568 patients were used to develop a CCSI composed of subjective and objective measures. Subjective measures included body mass index-adjusted weight loss grade, rate of weight loss, inflammation (neutrophil-to-lymphocyte ratio and C-reactive protein level), and prealbumin level. Objective measures included appetite status and physical status. Patients were diagnosed and stratified by the total CCSI score into 3 subgroups: no cachexia, mild or moderate cachexia, and severe cachexia. The CCSI grades showed good survival discrimination and were independently predictive of survival in multivariate analysis. Compared with the traditional Fearon criteria for diagnosing cancer cachexia, the CCSI was more accurate in predicting postoperative complications (net reclassification index [NRI], 2.8%; 95% CI, 0.0104-0.0456%), death (NRI, 10.68%; 95% CI, 0.0429-0.1708%), recurrence (NRI, 3.71%; 95% CI, 0.0082-0.0685%), and overall survival (NRI, 8.5%; 95% CI, 0.0219-0.1533%). The CCSI also had better discriminative ability than Fearon criteria in discriminating nutritional status, body composition, and systematic inflammation in patients with or without cachexia. A more detailed evaluation of a randomly selected subgroup (n = 1566) showed that CCSI grades had good discrimination of appetite and food intake status, physical function and muscle strength, symptom burden, and quality of life. CONCLUSIONS: The CCSI is a comprehensive and practical evaluation tool for cancer cachexia. It can predict postoperative outcomes and survival. The CCSI stages showed good discrimination when evaluating patients with cancer in terms of nutritional status, physical function, systematic inflammation, body composition, symptom burden, and quality of life.