A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors.

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is a devastating complication, resulting in early graft loss and reduced overall survival. Ultrasound is an established assessment method for HAO in patients following LT, especially those with complex hepatic artery reconstruction. AIM: To investigate the ultrasound characteristics and analyze the risk factors associated with HAO in patients after LT. METHODS: We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022. Fourteen patients diagnosed with acute HAO (A-HAO) by surgery and fifteen diagnosed with chronic HAO (C-HAO) were included. A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table. All patients underwent an ultrasonography examination. Parameters including resistance index (RI), peak systolic velocity (PSV), and portal vein velocity (PVV) were compared across the groups. Additionally, basic clinical data were collected for all patients, including gender, age, primary diagnosis, D-dimer concentration, total operation time, cold ischemia time, hot ischemia time, intraoperative blood loss and transfusion, intraoperative urine volume, infusion, model for end-stage liver disease (MELD) score, and whether complex hepatic artery reconstructions were performed. Furthermore, risk factors influencing HAO formation after LT were analyzed. RESULTS: Compared to the non-HAO group, PVV and RI were higher in the A-HAO group, while PSV was lower. Conversely, both PSV and RI were lower in the C-HAO group compared to the non-HAO group. The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase (GGT) level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group. However, there were no distinct differences between the two groups in D-dimer, MELD score, pre-occlusion alanine transaminase and aspartate transaminase levels, or intraoperative conditions. CONCLUSION: Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development. Additionally, complex hepatic artery reconstructions, defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries, constitute a risk factor for A-HAO. Besides, abnormal pre-occlusion GGT elevation is an important biochemical indicator. Therefore, ultrasound examination serves as an important tool for screening HAO, especially in patients with the identified risk factors.

Scavenging and release of REE and HFSE by Na-metasomatism in magmatic-hydrothermal systems.

Exploitable or potentially exploitable deposits of critical metals, such as rare-earth (REE) and high-field-strength elements (HFSE), are commonly associated with alkaline or peralkaline igneous rocks. However, the origin, transport and concentration of these metals in peralkaline systems remains poorly understood. This study presents the results of a mineralogical and geochemical investigation of the Na-metasomatism of alkali amphiboles and clinopyroxenes from a barren peralkaline granite pluton in NE China, to assess the remobilization and redistribution of REE and HFSE during magmatic-hydrothermal evolution. Alkali amphiboles and aegirine-augites from the peralkaline granites show evolutionary trends from sodic-calcic to sodic compositions, with increasing REE and HFSE concentrations as a function of increasing Na-index [Na#, defined as molar Na/(Na+Ca) ratios]. The Na-amphiboles (i.e., arfvedsonite) and aegirine-augites can be subsequently altered, or breakdown, to form hydrothermal aegirine during late- or post-magmatic alteration. Representative compositions analyzed by in-situ LA-ICPMS show that the primary aegirine-augites have high and variable REE (2194-3627 ppm) and HFSE (4194-16,862 ppm) contents, suggesting that these critical metals can be scavenged by alkali amphiboles and aegirine-augites. Compared to the primary aegirine-augites, the presentative early replacement aegirine (Aeg-I, Na# = 0.91-0.94) has notably lower REE (1484-1972) and HFSE (4351-5621) contents. In contrast, the late hydrothermal aegirine (Aeg-II, Na# = 0.92-0.96) has significantly lower REE (317-456 ppm) and HFSE (6.44-72.2 ppm) contents. Given that the increasing Na# from aegirine-augites to hydrothermal aegirines likely resulted from Na-metasomatism, a scavenging-release model can explain the remobilization of REE and HFSE in peralkaline granitic systems. The scavenging and release of REE and HFSE by Na-metasomatism provides key insights into the genesis of globally significant REE and HFSE deposits. The high Na-index of the hydrothermal aegirine might be useful as a geochemical indicator in the exploration for these critical-metals.

Clinical evaluation of new bone formation during limb lengthening in children using ultrasound combined with superb microvascular imaging.

Aims: Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children. Methods: In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs. Results: We categorized the new bone formation into three stages: stage I (early lengthening), in which there was no obvious callus formation on radiographs and ultrasound; stage II (lengthening), in which radiographs showed low-density callus formation with uneven distribution and three sub-stages could be identified on ultrasound: in Ia punctate callus was visible; in IIb there was linear callus formation which was not yet connected and in IIc there was continuous linear callus. In stage III (healing), the bone ends had united, the periosteum was intact, and the callus had disappeared, as confirmed on radiographs, indicating healed bone. A progressive increase in the number of vertical vessels was noted in the early stages, peaking during stages IIb and IIc, followed by a gradual decline (p < 0.001). Delayed healing involved patients with a prolonged stage IIa or those who regressed to stage IIa from stages IIb or IIc during lengthening. Conclusion: We found that the formation of new bone in paediatric patients undergoing limb lengthening could be reliably evaluated using ultrasound when combined with the radiological findings. This combination enabled an improved assessment of the prognosis, and adjustments to the lengthening protocol. While SMI offered additional insights into angiogenesis within the new bone, its role primarily contributed to the understanding of the microvascular environment rather than directly informing adjustments of treatment.

Current treatment of biliary Sphincter of Oddi Dysfunction.

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

The potential correlation between the succession of microflora and volatile flavor compounds during the production of Zhenba bacon.

Microbial composition plays an important role in the quality and flavor of bacon. The aims of this study were to detect bacterial community succession using high-throughput sequencing (HTS) and volatile flavor compound changes using gas chromatography-ion mobility spectrometry (GC-IMS) during the production of Zhenba bacon. The results showed that a total of 70 volatile compounds were detected. Among them, ketones, hydrocarbons, aldehydes, esters and alcohols were the main substances in the curing and smoking stages. In addition, the fungal abundance was greater than the bacterial abundance, and there was obvious succession of the microbial community with changes in fermentation time and processing technology. The main functional bacterial genera in the curing and smoking stages were Staphylococcus, Psychrobacter and Latilactobacillus, and the main fungal genera were Fusarium and Debaryomyces. Through correlation analysis, we found that pyrrole, 2-pentanol, methyl isobutyl ketone (MIBK) and ethyl acetate (EA) were significantly correlated with Staphylococcus, Psychrobacter, Pseudomonas and Myroides (p < 0.01), and it is speculated that they contribute significantly to flavor formation. The results of this study are helpful for understanding the microbial dynamics and characteristic volatile flavor compounds in Zhenba bacon, and provide new insights into the relationship between microorganisms and flavor through potential correlations.

Case report: Primary myelofibrosis presenting with portal hypertension mimicking cirrhosis.

Primary myelofibrosis (PMF) is an infrequent etiology of noncirrhotic portal hypertension (PH). In clinical settings, non-cirrhotic PH is often misdiagnosed as cirrhotic PH. This case report details a patient who exhibited recurrent esophageal variceal hemorrhage and was initially misdiagnosed with cirrhosis. Initially poised for liver transplantation, the patient's liver biopsy revealed no significant cirrhosis but showed signs of extramedullary hematopoiesis (EMH). Following the accurate diagnosis of PMF, the patient underwent standard treatment, leading to an absence of recurrent gastrointestinal hemorrhage due to esophageal varices for nearly three years.

Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.

BACKGROUND: Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences. METHODS: Three mice brains were collected from each group, including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD) and subsequently analyzed by label-free quantitative proteomics. RESULTS: The spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and the onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1, and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG). CONCLUSIONS: Utilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI's neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.

Altered COVID-19 immunity in children with asthma by atopic status.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. Objective: We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Methods: Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Results: Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second ≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Conclusion: Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

The effect of stent retriever mechanical thrombectomy combined with tirofiban in treating acute ischemic stroke.

OBJECTIVE: To analyze the effectiveness of stent retriever mechanical thrombectomy combined with tirofiban in treating acute ischemic stroke. METHODS: Markedly effective is defined as an SIS score of over 90, effective is indicated by an SIS score of between 50-90, and a score of below 50 suggests ineffective treatment results. RESULTS: ①The treatment's overall effectiveness in the observation group (91.30%) was significantly higher than that in the control group (75.56%) (p < 0.05). ②The vascular recanalization rate in the observation group (89.13%) was significantly higher than that in the control group (71.11%) (p < 0.05). ③The stent retrieval operation count (2.41 ± 0.23) was significantly lower in the observation group than in the control group (1.29 ± 0.16) (p < 0.05). ④ After treatment, the platelet aggregation rate (10.74 ± 3.95) and NIHSS scores (6.58 ± 1.04) were significantly lower, and the Barthel index (77.86 ± 7.21) was significantly higher in the observation group compared to the control group (26.47 ± 5.12, 7.75 ± 2.36, 68.12 ± 6.15) (p < 0.05). All platelet aggregation rate, NIHSS scores and Barthel Index showed significant improvement after treatment when compared to those before treatment (p < 0.05). CONCLUSION: The combined application of stent retriever mechanical thrombectomy and tirofiban in acute ischemic stroke treatment shows promising effectiveness. Compared to stent retriever alone, tirofiban adjunctive therapy enhances vascular recanalization, reduces retrieval procedures, shortens treatment duration, inhibits platelet aggregation, and improves neurological function recovery, daily living activities, and prognosis. Moreover, it doesn't significantly increase symptom-related risks.

Effects of Clip Anchoring on Preventing Migration of Fully Covered Self-Expandable Metal Stent in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.

Research status of pathogenesis of anxiety or depression after percutaneous coronary intervention and Traditional Chinese Medicine intervention.

ETHNIC PHARMACOLOGICAL RELEVANCE: Anxiety or depression after percutaneous coronary intervention (PCI) is a common clinical disease. Currently, conventional pharmacotherapy primarily involves the administration of anxiolytic or antidepressant medications in conjunction with anticoagulants, antiplatelet agents, and other cardiovascular drugs. However, challenges such as drug dependence, adverse reactions and related concerns persist in the treatment of this disease. Numerous pertinent studies have demonstrated that Traditional Chinese Medicine (TCM) exhibits significant therapeutic efficacy and distinctive advantages in managing post-PCI anxiety or depression. AIM OF THIS REVIEW: This review attempted to summarize the characteristics of TCM for treating anxiety or depression after PCI, including single Chinese herbs, Chinese medicine monomers, compound TCM prescriptions, TCM patented drugs, and other TCM-related treatment methods, focusing on the analysis of the relevant mechanism of TCM treatment of this disease. METHODS: By searching the literature on treating anxiety or depression after PCI with TCM in PubMed, Web of Science, CNKI, and other relevant databases, this review focuses on the latest research progress of TCM treatment of this disease. RESULTS: In the treatment of anxiety or depression after PCI, TCM exerts significant pharmacological effects such as anti-inflammatory, antioxidant, anti-anxiety or anti-depression, cardiovascular and cerebrovascular protection, and neuroprotection, mainly by regulating the levels of related inflammatory factors, oxidative stress markers, neurotransmitter levels, and related signaling pathways. TCM has a good clinical effect in treating anxiety or depression after PCI with individualized treatment. CONCLUSIONS: TCM has terrific potential and good prospects in the treatment of anxiety or depression after PCI. The main direction of future exploration is the study of the mechanism related to Chinese medicine monomers and the large sample clinical study related to compound TCM prescriptions.

Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures.

BACKGROUND: Hip fractures account for 23.8% of all fractures in patients over the age of 75 years. More than half of these patients are older than 80 years. Bipolar hemiarthroplasty (BHA) was established as an effective management option for these patients. Various approaches can be used for the BHA procedure. However, there is a high risk of postoperative dislocation. The conjoined tendon-preserving posterior (CPP) lateral approach was introduced to reduce postoperative dislocation rates. AIM: To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients. METHODS: We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA. The patients were followed up for at least 1 year. Among the 80 patients, 57 (71.3%) were female. The time to operation averaged 2.3 d (range: 1-5 d). The mean age was 80.5 years (range: 67-90 years), and the mean body mass index was 24.9 kg/m2 (range: 17-36 kg/m2). According to the Garden classification, 42.5% of patients were type Ⅲ and 57.5% of patients were type Ⅳ. Uncemented bipolar hip prostheses were used for all patients. Torn conjoined tendons, dislocations, and adverse complications during and after surgery were recorded. RESULTS: The mean postoperative follow-up time was 15.3 months (range: 12-18 months). The average surgery time was 52 min (range: 40-70 min) with an average blood loss of 120 mL (range: 80-320 mL). The transfusion rate was 10% (8 of 80 patients). The gemellus inferior was torn in 4 patients (5%), while it was difficult to identify in 2 patients (2.5%) during surgery. The posterior capsule was punctured by the fractured femoral neck in 3 patients, but the conjoined tendon and the piriformis tendon remained intact. No patients had stem varus greater than 3 degrees or femoral fracture. There were no patients with stem subsidence more than 5 mm at the last follow-up. No postoperative dislocations were observed throughout the follow-up period. No significance was found between preoperative and postoperative mean Health Service System scores (87.30 ± 2.98 vs 86.10 ± 6.10, t = 1.89, P = 0.063). CONCLUSION: The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications. For surgeons familiar with the posterior lateral approach, there is no need for additional surgical instruments, and it does not increase surgical difficulty.

Prognostic value of ultrasound in early arterial complications post liver transplant.

Liver transplantation is the primary therapeutic intervention for end-stage liver disease. However, vascular complications, particularly those involving the hepatic artery, pose significant risks to patients. The clinical manifestations associated with early arterial complications following liver transplantation are often nonspecific. Without timely intervention, these complications can result in graft failure or patient mortality. Therefore, early diagnosis and the formulation of an optimal treatment plan are imperative. Ultrasound examination remains the predominant imaging modality for detecting complications post liver transplantation. This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these conditions. Overall, ultrasound offers the advantages of convenience, safety, effectiveness, and non-invasiveness. It enables real-time, dynamic, and precise evaluation, making it the preferred diagnostic method for post-liver transplantation assessments.

Correction of anterior bowing complicating tibial osteofibrous dysplasia in preadolescents by osteotomy and telescopic nailing without lesional resection: a preliminary study of four-case reports.

BACKGROUND: Osteofibrous dysplasia (OFD) occurs most frequently in the tibia and may result in deformity and pathological fracture. Surgical treatment such as curettage or segment excision has been performed but remains controversial due to high complication rates and surgical burden. This study introduces a new method to manage OFD with anterior bowing of the tibia using minimally invasive tibial osteotomy and telescopic rod (TR) osteosynthesis without extensive lesion resection. METHODS: A retrospective study of 4 children with OFD and tibia bowing deformity treated with minimally invasive tibial wedge osteotomy and TR fixation between January 2015 and November 2020 was performed. Results including bone healing, complications, function based on MSTS score, and recurrance of deformity were assessed. RESULTS: The median follow-up was 29 months. Radiographs showed the median time for union was 3 months. There were no instances of refracture or recurrence of deformity. The mean post-operative MSTS score was significantly higher than preoperative score. CONCLUSIONS: This method avoids large bone defects and reconstructive procedures. It is an effective and minimally invasive approach for managing anterior bowing deformity secondary to OFD while improving function and quality of life. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

[Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells].

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 µg/L), moderate (10 µg/L), and high (100 µg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid ß-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid ß-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid ß-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.

Enhancing physiological recovery and subsequent exercise performance in the heat using a phase-change material cooling blanket.

This study aimed to assess the effect of a phase-change material (PCM) cooling blanket for cooling between exercise bouts on recovery of physiological parameters and subsequent exercise performance in the heat. Eighteen male volunteers were recruited to participate in human trials involving two exhaustive treadmill running bouts (Bout1 for 3 km and Bout2 for 1.5 km) in a climate chamber (temperature = 33 °C; relative humidity = 40%). Participants were randomly subjected to one of two cooling conditions for a 10-min period between exercise bouts: CON: natural cooling; 10-min PCM: with a PCM cooling blanket for 10 min. Several physiological parameters including mean skin temperature (Tskin), oral temperature (Toral), core temperature (Tcore), heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), peripheral capillary oxygen saturation (SpO2), average running speed and rating of perceived exertion (RPE) scale score were analyzed. The results showed that compared to the CON group, participants in the 10-min PCM group had a significant lower Tskin, Tcore, HR and RR at post-cooling, as well as greater reductions in mean skin temperature (ΔTskin) and core temperature (ΔTcore) from post-Bout1 to post-cooling. Additionally, the 10-min PCM group exhibited significantly lower peak Tcore, peak HR and RPE scale score during Bout2, while the average running speed during Bout2 was significantly higher. The present study suggests that cooling with a PCM cooling blanket can enhance physiological recovery and subsequent exercise performance in the heat.

Serum Cell-Free DNA-based Detection of Mycobacterium avium Complex Infection.

Rationale: Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) pulmonary disease (PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A clustered regularly interspaced short palindromic repeats (CRISPR)-based assay that measures MAC cell-free DNA (cfDNA) concentrations in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment. Objectives: To develop and optimize a CRISPR MAC assay for MAC infection detection and to evaluate its diagnostic and prognostic performance in two MAC disease cohorts. Methods: MAC cfDNA serum concentrations were measured in individuals with diagnoses of MAC disease or who had bronchiectasis or chronic obstructive pulmonary disease diagnoses without histories of NTM PD or NTM-positive sputum cultures. Diagnostic performance was analyzed using pretreatment serum from two cohorts. Serum MAC cfDNA changes during MAC PD treatment were evaluated in a subset of patients with MAC PD who received macrolide-based multidrug regimens. Measurements and Main Results: The CRISPR MAC assay detected MAC cfDNA in MAC PD with 97.6% (91.6-99.7%) sensitivity and 97.6% (91.5-99.7%) specificity overall. Serum MAC cfDNA concentrations markedly decreased after MAC-directed treatment initiation in patients with MAC PD who demonstrated MAC culture conversion. Conclusions: This study provides preliminary evidence for the utility of a serum-based CRISPR MAC assay to rapidly detect MAC infection and monitor the response to treatment.

Impact of endoplasmic reticulum stress on chondrocyte apoptosis in rat model of DDH.

Developmental dysplasia of the hip (DDH) is a developmental disorder characterized by acetabular dysplasia leading to early osteoarthritis. This study examines the role of endoplasmic reticulum stress (ERS) in chondrocyte apoptosis and cartilage degeneration within a DDH model. In the rat model of DDH, created using a swaddling technique, significant deformities in the femoral head and acetabulum were observed, alongside an upregulation of matrix metalloproteinase-13 in acetabular cartilage. We also noted increased levels of apoptosis and ERS-related factors in the acetabular cartilage of DDH models. Additionally, rat chondrocytes exposed to high-magnitude cyclic tensile strain (CTS, 1 Hz, 10% equibiaxial strain) in vitro exhibited elevated ERS and increased apoptosis. Importantly, treatment with the ERS inhibitor 4-phenylbutyric acid effectively suppressed apoptosis induced by CTS in chondrocytes. Our findings suggest that ERS contributes to the upregulation of apoptosis-related factors in chondrocytes within the DDH model, indicating the potential of ERS modulation as a therapeutic approach for DDH-related cartilage degeneration.