Morphological Brain Networks of White Matter: Mapping, Evaluation, Characterization, and Application.

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good-to-excellent test-retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co-expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co-expression, and is associated with serotonergic system-related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease.

Development and reproduction of Scirtothrips dorsalis (Thysanoptera: Thripidae) on six host plant species.

Host plants can strongly influence the population performance of insects. Here, we investigated the development, survival, and oviposition of Scirtothrips dorsalis Hood on 6 host plants-Camellia sinensis ( L.) Kuntze (Ericales: Theaceae), Rosa chinensis Jacq. (Rosales: Rosaceae), Capsicum annuum L. (Solanales: Solanaceae), Eustoma grandiflorum (Hook.) G.Don (Gentianales: Gentianaceae), Glycine max (L.) Merr. (Fabales: Fabaceae), and Cucumis sativus L. (Cucurbitales: Cucurbitaceae), and constructed life tables for S. dorsalis on each plant. Significant differences in S. dorsalis development on the host species were observed. The mean developmental period from egg to adult was 11.45 ±â€…0.12 days, 11.24 ±â€…0.13 days, 12.08 ±â€…0.15 days, 12.28 ±â€…0.12 days, 12.67 ±â€…0.10 days, and 13.03 ±â€…0.11 days on C. sinensis, R. chinensis, C. annuum, E. grandiflorum, G. max, and C. sativus, respectively. Significant differences in survival of S. dorsalis were observed, namely, C. sinensis ≈ R. chinensis > E. grandiflorum ≈ C. annuum > G. max > C. sativus. The highest and lowest fecundities of S. dorsalis were recorded on R. chinensis (60.44 ±â€…1.53) and C. sativus (28.64 ±â€…1.02), respectively. Both of the net reproductive rate (R0) and intrinsic rate of increase (rm) of S. dorsalis were the highest on R. chinensis, with the values of 27.63 ±â€…0.58 and 0.142 ±â€…0.002, respectively; while the lowest on C. sativus, with the values of 8.81 ±â€…0.12 and 0.092 ±â€…0.003, respectively. Thus, R. chinensis was found to be the most suitable host, but C. sativus was the least suitable, for population development of S. dorsalis. Our results provide important information for the key control of S. dorsalis among different host plants.

Serum anion gap at admission predicts all-cause mortality in critically ill patients with cirrhosis: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: The primary objective of this study was to evaluate admission serum Anion Gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis. MATERIALS AND METHODS: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes. RESULTS: Both cohorts showed strong parameter similarity (P > 0.05). High AG were associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (HR: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable to established scoring systems. CONCLUSION: Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.

Semirecumbent Positioning During Anesthesia Recovery and Postoperative Hypoxemia: A Randomized Clinical Trial.

Importance: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use. Objective: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position. Design, Setting, and Participants: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete. Interventions: Patients were randomized to 1 of the following positions at the end of the operation until leaving the postanesthesia care unit: supine (group S), 15° SRP (group F), or 30° SRP (group T). Main Outcomes and Measures: The primary outcome was the incidence of postoperative hypoxemia in the postanesthesia care unit. Severe hypoxemia was also evaluated. Results: Out of 700 patients (364 men [52.0%]; mean [SD] age, 47.8 [11.3] years), 233 were randomized to group S (126 men [54.1%]; mean [SD] age, 48.2 [10.9] years), 233 to group F (122 men [52.4%]; mean [SD] age, 48.1 [10.9] years), and 234 to group T (118 women [50.4%]; mean [SD] age, 47.2 [12.1] years). Postoperative hypoxemia differed significantly among the 3 groups (group S, 109 of 233 [46.8%]; group F, 105 of 233 [45.1%]; group T, 76 of 234 [32.5%]; P = .002). This difference was statistically significant for groups T vs S (risk ratio [RR], 0.69 [95% CI, 0.55-0.87]; P = .002) and groups T vs F (RR, 0.72 [95% CI, 0.57-0.91]; P = .007), but not for groups F vs S (RR, 0.96 [95% CI, 0.79-1.17]; P = .78). Severe hypoxemia also differed among the 3 groups (group S, 61 of 233 [26.2%]; group F, 53 of 233 [22.7%]; group T, 36 of 234 [15.4%]; P = .01). This difference was statistically significant for groups T vs S (RR, 0.59 [95% CI, 0.41-0.85]; P = .005). Conclusions and Relevance: In this randomized clinical trial of SRP during anesthesia recovery in patients undergoing laparoscopic upper abdominal surgery, postoperative hypoxemia was significantly reduced in group T compared with group F or group S. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100045087.

A bioinspired heterostructured nanochannel based on dendrimer-gold network and aluminum oxide arrays for sensitive detection of miRNA.

BACKGROUND: MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection. RESULTS: In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples. SIGNIFICANCE: This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.

Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity.

Background and aims: High-dose Obeticholic acid exhibits promise for non-alcoholic fatty liver disease (NAFLD) treatment but can induce lipotoxicity. Our study sought to understand this mechanism and propose a solution. Approach and Results: In a non-alcoholic fatty liver disease (NAFLD) model induced by a high-fat diet in FXR-/- mice, we pinpointed that FXR regulated the expression of ACOX1 through RNA-Seq analysis. In the livers of FXR-/- mice, both ACOX1 mRNA and protein expression notably decreased. In both HL-7702 and HEP-G2 cells, the silencing of FXR through shRNA plasmids decreased ACOX1 expression, while FXR activation with GW4064 increased it. These effects were reversible with the ACOX1-specific inhibitor, 10,12-Tricosadiynoic acid. In the NAFLD model of FXR-/- mice, The activation of ACOX1 is correlated with elevated serum LDL, triglycerides, and aggravated hepatic steatosis. However, the combination of 10,12-Tricosadiynoic acid with low-dose obeticholic acid effectively treated hepatic steatosis, reducing LDL levels in the NAFLD model of wild-type mice. This combination therapy demonstrated efficacy comparable to high-dose obeticholic acid alone. Notably, the combined drug regimen treats hepatic steatosis by inhibiting the IL-1ß and α-SMA pathways in NAFLD. Conclusion: Combining ACOX1-specific inhibitors with low-dose obeticholic acid effectively treats high-fat diet-induced hepatic steatosis and reduces serum LDL. This approach enhances the therapeutic effects of obeticholic acid and mitigates its lipotoxicity by inhibiting the IL-1ß and α-SMA pathways.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Self-healing polyacrylates based on dynamic disulfide and quadruple hydrogen bonds.

Herein, a self-healing polyacrylate system was successfully prepared by introducing crosslinking agents containing disulfide bonds and monomers capable of forming quadruple hydrogen bonds through free radical copolymerization. This polymer material exhibited good toughness and self-healing properties through chemical and physical dual dynamic networks while maintaining excellent mechanical properties, which expanded the development path of self-healing acrylate materials. Compared to uncrosslinked and single dynamically crosslinked polymers, its elongation at break was as high as 437%, and its tensile strength was 5.48 MPa. Due to the presence of dual reversible dynamic bonds in the copolymer system, good self-healing was also achieved at 60 °C. In addition, differential scanning calorimetry and thermogravimetric analysis measurements confirmed that the thermal stability and glass transition temperature of the material were improved owing to the presence of physical and chemical cross-linking networks.

Good clinical outcomes of anterior cruciate ligament reconstruction in patients over 60 years of age.

PURPOSE: To evaluate the clinical outcomes following arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) in patients over 60 years and to investigate the potential impact of preoperative osteoarthritis (OA) on these outcomes. METHODS: A retrospective study included ACL-injured patients over 60 years who underwent primary arthroscopic ACLR between 2010 and 2020. The Lysholm score and the International Knee Documentation Committee (IKDC) score were assessed preoperatively and at the final follow-up. The Tegner activity scale was performed to evaluate patients' activity levels. Data on return to sports, patient satisfaction, subsequent injuries and complications were collected. Preoperative radiographs were used to grade OA according to the Kellgrene-Lawrence classification. Correlation analysis between OA and clinical outcomes was performed. The rates of achieving the minimal clinically significant difference and patient-acceptable symptoms state were documented. RESULTS: A total of 37 patients were included in this study. The mean age at surgery was 62.3 ± 2.3 years, with a mean follow-up of 6.3 ± 3.2 years (range: 2.1-12.4). Patients showed statistically significant (all p < 0.001) improvements in the mean IKDC (38.9 ± 9.4-66.8 ± 12.5), Lysholm (48.8 ± 15.4-83.0 ± 12.8) and Tegner (1-3) scores. Fourteen patients (37.8%) returned to sports. No correlation was observed between the degree of preoperative OA and clinical outcomes (n.s.). CONCLUSION: Patients over 60 years with symptomatic ACL-deficient knees could benefit from ACLR, even when mild to moderate OA is present preoperatively. LEVEL OF EVIDENCE: Level IV.

Evaluation of the in vitro and in vivo antimicrobial activity of alkaloids prepared from Chelidonium majus L. using MRSA- infected C. elegans as a model host.

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.

[Comparison of the early analgesic efficacy of three different drugs after anterior cruciate ligament reconstruction].

OBJECTIVE: The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early stage of autologous tendon reconstruction of the anterior cruciate ligament (ACL) of the knee joint were compared. METHODS: Retrospective analysis of postoperative pain and drug analgesia in 45 patients performed by the same group from November 2018 to February 2019. The random area group design was divided into two groups according to whether ACL rupture was combined with meniscal injury, group A was 24 patients with ACL reconstruction of knee joint and group B was 21 patients with ACL fracture combined with meniscus injury. The two groups were divided into three subgroups respectively according to the actual treatment of postoperative analgesic drugs received by the patients, including 4 cases of compound aminopyrine phenacetin tablets, 11 cases of oral tramcontin, 9 cases of intramuscular dolantin combined with phenergan in group A; 3 cases of compound aminopyrine phenacetin tablets, 10 cases of oral tramcontin, and 8 cases of intramuscular dolantin combined with phenergan in group B. When the early postoperative patients complain about pain and actively ask for analgesia. When the patients complained about pain after the operation and actively asked for analgesia, they were randomly given painkillers, tramcontin or dolantin combined with phenergan to relieve pain. Pain visual analogue scale (VAS) was used to evaluate pain relief and observe the occurrence of adverse reactions. RESULTS: There were no significant dif-ferences in gender, age, body mass index, and time of hospital stay between the two groups of patients (P > 0.05). In the patients who used tramcontin and dolantin combined with phenergan to relieve pain judging by VAS score before and 1 h after taking the drug, it was found that the pain situation of the patient was significantly relieved, and the difference before and after taking the drug had statistical significance (P < 0.05). Pairwise comparisons of the three drugs applied in the two groups showed significantly greater pain relief in the dolantin combined with phenergan group than in the remaining two drugs. There was no significant difference (P > 0.05). Dolantin was prone to nausea and vomiting, but the application of phenergan was also used to reduce side effects. In terms of adverse reactions, only 1 case of nausea occurred in the tramcontin group for simple ACL reconstruction, and none of the patients in the other groups showed serious complications and allergic reactions. CONCLUSION: Whether in cruciate ligament reconstruction alone or combined with meniscus molding or suture, compound aminopyrine phenacetin tablets, tramcontin, dolantin combined with phenergan can effectively relieve pain. Among the three drugs, dolantin caused the largest pain relief. At the same time, the combination of phenergan effectively reduced the adverse reactions, such as vomiting and nausea, and increased the drug safety.

Arthroscopically Assisted Double-Bundle Medial Patellofemoral Ligament Augmentation With Physeal-Sparing Suture Fixation for Recurrent Patellar Dislocation in Skeletally Immature Patients.

Recurrent patellar dislocation is a common patellofemoral disease that affects active adolescents. The optimal surgical treatment of recurrent patellar dislocation in skeletally immature patients remains controversial. This Technical Note describes an arthroscopically assisted double-bundle medial patellofemoral ligament (MPFL) augmentation. Orthocord suture, with ideal strength and partial bioabsorbable characteristics, is used as the stabilizer to augment and protect the native MPFL during its biological healing. Under an arthroscope, patellar tunnels are created with Kirshner wire at the upper third point of the medial articular margin and the midpoint of the proximal articular margin. A physeal-sparing transosseous suture fixation technique is applied at the femoral attachment. Two femoral tunnels are made with half-circle cutting needle, which is pierced into the femoral origin of the MPFL and exits the posterior femoral cortex. After dynamic assessments of knee range of motion and patellofemoral congruence, free ends of the Orthocord suture bundle are tied together at the external opening of the femoral tunnel. Transosseous suture fixation balances the requirements of anatomic restoration, reliable fixation, and physeal preservation, and thus may provide a promising alternative to current algorithm of addressing recurrent patellar dislocation in pediatric population.

An in situ forming gel co-loaded with pirarubicin and celecoxib inhibits postoperative recurrence and metastasis of breast cancer.

Surgical removal combined with postoperative chemotherapy is still the mainstay of treatment for most solid tumors. Although chemotherapy reduces the risk of recurrence and metastasis after surgery, it may produce serious adverse effects and impair patient compliance. In situ drug delivery systems are promising tools for postoperative cancer treatment, improving drug delivery efficiency and reducing side effects. Herein, an injectable phospholipid-based in situ forming gel (IPG) was prepared for the co-delivery of antitumor agent pirarubicin (THP) and cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) in the surgical incision, and the latter are used extensively in adjuvant chemotherapy for cancer. After injection, the IPG co-loaded with THP and CXB (THP-CXB-IPG) underwent spontaneous phase transition and formed a drug reservoir that fitted the irregular surgical incisions perfectly. In vitro drug release studies and in vivo pharmacokinetic analysis had demonstrated the sustained release behaviors of THP-CXB-IPG. The in vivo therapeutic efficacy was evaluated in mice that had undergone surgical resection of breast cancer, and the THP-CXB-IPG showed considerable inhibition of residual tumor growth after surgery and reduced the incidence of pulmonary metastasis. Moreover, it reduced the systemic toxicity of chemotherapeutic agents. Therefore, THP-CXB-IPG can be a promising candidate for preventing postoperative recurrence and metastasis.

Multimodal ultrasonic manifestations of secretory carcinoma of the breast: A case description.

 Secretory carcinoma of the breast (SCB) is a rare and specific type of breast cancer. Owing to its rarity, the number of SCB reports available is limited, with most of them focusing on clinical and pathological characteristics but no reports on its multimodal ultrasound (US) features. Thus, we present a rare case of SCB, retrospectively analyzing manifestations of US and contrast-enhanced US, as well as its pathological basis, aiming to enhance the understanding of US image features of SCB and provide more valuable information for clinical diagnosis. Moreover, the treatment strategy adopted for this patient may serve as a template for future management of SCB.

Gold Nanoparticles in Neurological Diseases: A Review of Neuroprotection.

This review explores the diverse applications of gold nanoparticles (AuNPs) in neurological diseases, with a specific focus on Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The introduction highlights the pivotal role of neuroinflammation in these disorders and introduces the unique properties of AuNPs. The review's core examines the mechanisms by which AuNPs exert neuroprotection and anti-neuro-inflammatory effects, elucidating various pathways through which they manifest these properties. The potential therapeutic applications of AuNPs in AD are discussed, shedding light on promising avenues for therapy. This review also explores the prospects of utilizing AuNPs in PD interventions, presenting a hopeful outlook for future treatments. Additionally, the review delves into the potential of AuNPs in providing neuroprotection after strokes, emphasizing their significance in mitigating cerebrovascular accidents' aftermath. Experimental findings from cellular and animal models are consolidated to provide a comprehensive overview of AuNPs' effectiveness, offering insights into their impact at both the cellular and in vivo levels. This review enhances our understanding of AuNPs' applications in neurological diseases and lays the groundwork for innovative therapeutic strategies in neurology.

Two-stage association study of mitochondrial DNA variants in allergic rhinitis.

BACKGROUND: Correlations between mitochondrial DNA (mtDNA) and allergic rhinitis (AR) have not been reported before. This study aimed to better understand the mitochondrial genome profile with AR and to investigate the associations between AR in China and the mitochondrial genome at a single variant and gene level. METHODS: Mitochondrial sequencing was conducted on a total of 134 unrelated individual subjects (68 patients with AR, 66 healthy controls) at discovery stage. Heteroplasmy was analyzed using the Mann-Whitney U test. Sequence kernel association tests (SKAT) were conducted to study the association between mitochondrial genes and AR. Single-variant analysis was performed using logistic regression analysis and further validated in 120 subjects (69 patients with AR, 51 healthy controls). Candidate genes were further explored based on differences in mRNA and protein abundance in nasal mucosal tissue. RESULTS: In the discovery stage, 886 variants, including 836 SNV and 50 indels, were identified with mitochondrial sequencing. No statistically significant differences were identified for the mitochondrial heteroplasmy or SKAT analysis between these two groups after applying a Boferroni correction. One nonsynonymous variants, rs3135028 (MT8584.G/A) in ATP6, was related to a reduced risk of AR in both the discovery and validation cohorts. Furthermore, mRNA levels of MT-ATP6 in nasal mucosal tissue were significantly lower in AR individuals than in controls (P < 0.05). CONCLUSIONS: In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.

Femoral Tunnel Malposition, Increased Lateral Tibial Slope, and Decreased Notch Width Index Are Risk Factors for Non-Traumatic Anterior Cruciate Ligament Reconstruction Failure.

PURPOSE: To identify risk factors for patients who sustain nontraumatic anterior cruciate ligament reconstruction (ACLR) failure. METHODS: A retrospective analysis was performed on patients undergoing primary or revision ACLR in our institution between 2010 and 2018. Patients sustaining insidious-onset knee instability without history of trauma were identified as nontraumatic ACLR failure and assigned to the study group. The control group of subjects who showed no evidence of ACLR failure with minimum 48-month follow-up were matched in a 1:1 ratio based on age, sex, and body mass index. Anatomic parameters including tibial slope (lateral [LTS], medial [MTS]); tibial plateau subluxation (lateral [LTPsublx], medial [MTPsublx]); notch width index (NWI); and lateral femoral condyle ratio were measured with magnetic resonance imaging or radiography. Graft tunnel position was assessed using 3-dimensional computed tomography and reported in 4 dimensions: deep-shallow ratio (DS ratio) and high-low ratio for femoral tunnel, anterior-posterior ratio and medial-lateral ratio for tibial tunnel. Interobserver and intraobserver reliability were evaluated by the intraclass correlation coefficient (ICC). Patients' demographic data, surgical factors, anatomic parameters, and tunnel placements were compared between the groups. Multivariate logistic regression and receiver operating characteristic curve analysis was used to discriminate and assess the identified risk factors. RESULTS: A total of 52 patients who sustained nontraumatic ACLR failure were included and matched with 52 control subjects. Compared to patients with intact ACLR, those who sustained nontraumatic ACLR failure showed significantly increased LTS, LTPsublx, MTS, and deceased NWI (all P < .001). Moreover, the average tunnel position in the study group was significantly more anterior (P < .001) and superior (P = .014) at the femoral side and more lateral (P = .002) at the tibial side. Multivariate regression analysis identified LTS (odds ratio [OR] = 1.313; P = .028), DS ratio (OR = 1.091; P = .002), and NWI (OR = 0.813; P = .040) as independent predictors of nontraumatic ACLR failure. LTS appeared to be the best independent predictive factor (area under the curve [AUC] = 0.804; 95% confidence interval [CI], 0.721-0.887), followed by DS ratio (AUC = 0.803; 95% CI, 0.717-0.890), and NWI (AUC = 0.756; 95% CI, 0.664-0.847). The optimal cutoff values were 6.7° for increased LTS (sensitivity = 0.615, specificity = 0.923); 37.4% for increased DS ratio (sensitivity = 0.673, specificity = 0.885); and 26.4% for decreased NWI (sensitivity = 0.827, specificity = 0.596). Intraobserver and interobserver reliability was good to excellent, with ICCs ranging from 0.754 to 0.938 for all radiographical measurements. CONCLUSIONS: Increased LTS, decreased NWI, and femoral tunnel malposition are predictive risk factors for nontraumatic ACLR failure. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Medial Patellofemoral Complex Reconstruction (Combined Reconstruction of Medial Patellofemoral Ligament and Medial Quadriceps Tendon-Femoral Ligament) With Semitendinosus Autograft Resulted in Similar Clinical and Radiographic Outcomes to Medial Patellofemoral Ligament Reconstruction in Treating Recurrent Patellar Dislocation.

PURPOSE: To compare clinical and radiographic outcomes of medial patellofemoral ligament reconstruction (MPFL-R) and medial patellofemoral complex reconstruction (MPFC-R) for recurrent patellar dislocation. Outcome measures were compared based on the Insall-Salvati index. METHODS: Patients who were diagnosed with recurrent patellar dislocation and underwent either MPFL-R or MPFC-R (combined reconstruction of MPFL and medial quadriceps tendon-femoral ligament) were retrospectively analyzed. Group allocation was based on surgical procedure and patient characteristics were collected. Clinical assessments included patient-reported outcome measures (PROMs) and return-to-sports rates. Minimal clinically important difference analysis was performed. A subgroup analysis of PROMs was carried out between patients with an Insall-Salvati index ≤1.2 versus >1.2. The patellar tilt angle, lateral patellar displacement, and bisect offset ratio were measured pre- and postsurgery. Functional failures and complications were assessed. RESULTS: Overall, 70 patients (72 knees) in the MPFL-R group and 58 patients (61 knees) in the MPFC-R group were included. Patient characteristics were comparable between the groups. At a minimum follow-up of 24 (mean, 50.6 ± 22.1) months, all PROMs were substantially improved (P < .001), without significant intergroup differences. The percentages of patients reaching the minimal clinically important difference were similar after MPFL-R and MPFC-R: 98.6% versus 93.4% (International Knee Documentation Committee), 97.2% versus 98.4% (Lysholm), 98.6% versus 100% (Kujala), and 77.8% versus 72.1% (Tegner). The subgroup analysis based on patellar height and the return-to-sport rates also suggested comparable results. Radiographic evaluation demonstrated significantly smaller lateral patellar displacements (P = .004) and bisect offset ratios (P < .001) but similar patellar tilt angles after MPFC-R. Four (5.6%) patients receiving MPFL-R and 2 (3.3%) patients receiving MPFC-R reported recurrence of functional instability, without statistically significant difference. CONCLUSIONS: MPFC-R resulted in similar overall clinical and radiographic outcomes to MPFL-R in treating recurrent patellar dislocation. MPFC-R might not provide additional benefits for patients with an Insall-Salvati index >1.2. LEVEL OF EVIDENCE: Level IV, therapeutic, retrospective cohort study.

Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases.

Inflammation is a natural host defense mechanism that protects the body from pathogenic microorganisms. A growing body of research suggests that inflammation is a key factor in triggering other diseases (lung injury, rheumatoid arthritis, etc.). However, there is no consensus on the complex mechanism of inflammatory response, which may include enzyme activation, mediator release, and tissue repair. In recent years, p38 MAPK, a member of the MAPKs family, has attracted much attention as a central target for the treatment of inflammatory diseases. However, many p38 MAPK inhibitors attempting to obtain marketing approval have failed at the clinical trial stage due to selectivity and/or toxicity issues. In this paper, we discuss the mechanism of p38 MAPK in regulating inflammatory response and its key role in major inflammatory diseases and summarize the synthetic or natural products targeting p38 MAPK to improve the inflammatory response in the last five years, which will provide ideas for the development of novel clinical anti-inflammatory drugs based on p38 MAPK inhibitors.