The novel regulator HdrR controls the transcription of the heterodisulfide reductase operon hdrBCA in Methanosarcina barkeri.

Methanogenic archaea play a key role in the global carbon cycle because these microorganisms remineralize organic compounds in various anaerobic environments. The microorganism Methanosarcina barkeri is a metabolically versatile methanogen, which can utilize acetate, methanol, and H2/CO2 to synthesize methane. However, the regulatory mechanisms underlying methanogenesis for different substrates remain unknown. In this study, RNA-seq analysis was used to investigate M. barkeri growth and gene transcription under different substrate regimes. According to the results, M. barkeri showed the best growth under methanol, followed by H2/CO2 and acetate, and these findings corresponded well with the observed variations in genes transcription abundance for different substrates. In addition, we identified a novel regulator, MSBRM_RS03855 (designated as HdrR), which specifically activates the transcription of the heterodisulfide reductase hdrBCA operon in M. barkeri. HdrR was able to bind to the hdrBCA operon promoter to regulate transcription. Furthermore, the structural model analyses revealed a helix-turn-helix domain, which is likely involved in DNA binding. Taken together, HdrR serves as a model to reveal how certain regulatory factors control the expression of key enzymes in the methanogenic pathway.IMPORTANCEThe microorganism Methanosarcina barkeri has a pivotal role in the global carbon cycle and contributes to global temperature homeostasis. The consequences of biological methanogenesis are far-reaching, including impacts on atmospheric methane and CO2 concentrations, agriculture, energy production, waste treatment, and human health. As such, reducing methane emissions is crucial to meeting set climate goals. The methanogenic activity of certain microorganisms can be drastically reduced by inhibiting the transcription of the hdrBCA operon, which encodes heterodisulfide reductases. Here, we provide novel insight into the mechanisms regulating hdrBCA operon transcription in the model methanogen M. barkeri. The results clarified that HdrR serves as a regulator of heterodisulfide reductase hdrBCA operon transcription during methanogenesis, which expands our understanding of the unique regulatory mechanisms that govern methanogenesis. The findings presented in this study can further our understanding of how genetic regulation can effectively reduce the methane emissions caused by methanogens.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Usefulness of risk assessment tools in predicting hemodynamic outcome after balloon pulmonary angioplasty: a comparative analysis.

OBJECTIVES: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. METHODS: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. RESULTS: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). CONCLUSION: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.

Kinetic pathway of HIV-1 TAR cotranscriptional folding.

The Trans-Activator Receptor (TAR) RNA, located at the 5'-end untranslated region (5' UTR) of the human immunodeficiency virus type 1 (HIV-1), is pivotal in the virus's life cycle. As the initial functional domain, it folds during the transcription of viral mRNA. Although TAR's role in recruiting the Tat protein for trans-activation is established, the detailed kinetic mechanisms at play during early transcription, especially at points of temporary transcriptional pausing, remain elusive. Moreover, the precise physical processes of transcriptional pause and subsequent escape are not fully elucidated. This study focuses on the folding kinetics of TAR and the biological implications by integrating computer simulations of RNA folding during transcription with nuclear magnetic resonance (NMR) spectroscopy data. The findings reveal insights into the folding mechanism of a non-native intermediate that triggers transcriptional pause, along with different folding pathways leading to transcriptional pause and readthrough. The profiling of the cotranscriptional folding pathway and identification of kinetic structural intermediates reveal a novel mechanism for viral transcriptional regulation, which could pave the way for new antiviral drug designs targeting kinetic cotranscriptional folding pathways in viral RNAs.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Blood urea nitrogen to serum albumin ratio as a new indicator of disease severity and prognosis in idiopathic pulmonary artery hypertension.

BACKGROUND: Emerging evidence has shown that the blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study investigated the associations between BAR and functional status, echocardiographic findings, hemodynamics, and long-term outcomes among patients with IPAH. METHODS: This study included consecutive patients who underwent right heart catheterization (RHC) and were diagnosed with IPAH between January 2013 and January 2018 at Fuwai Hospital. The primary outcome was the worsening of clinical symptoms. Spearman correlation coefficients were used to evaluate the association between the BAR and established markers of IPAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine BAR's optimal cut-off and predictive performance. Kaplan-Meier analysis and Cox proportional hazard models assessed the relationship between BAR and clinical worsening. RESULTS: A total of 340 patients with IPAH were included in this study. BAR correlated with well-validated variables that reflected the severity of IPAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, mixed venous oxygen saturation, and cardiac index. Kaplan-Meier curves indicated that patients with BAR＞3.80 had a significantly higher clinical worsening rate (log-rank test, P < 0.001) than those with BAR≤3.80. Multivariate Cox analysis showed that BAR could independently predict clinical worsening [hazard ratio(HR):2.642, 95 % confidence interval (CI):1.659-4.208, P < 0.001]. In addition, BAR provided additional predictive value for the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk assessment score. CONCLUSIONS: BAR reflects disease severity and is independently associated with the prognosis of patients with IPAH.

[Comparative study of external fixator combined with Kirschner wire fixation and Kirschner wires fixation in treatment of cubitus varus deformity in children].

Objective: To analyze the effectiveness comparison of external fixator combined with Kirschner wire fixation and Kirschner wire fixation in the treatment of cubitus varus deformity in children. Methods: A retrospective case-control study was conducted to collect 36 children of postoperative supracondylar humerus fracture complicating cubitus varus deformity between January 2018 and July 2022. Among them, 17 cases were treated with distal humeral wedge osteotomy external fixation combined with Kirschner wire fixation (observation group), and 19 cases were treated with distal humeral wedge osteotomy and Kirschner wire fixation (control group). The baseline data including age, gender, deformity side, time from fracture to operation, carrying angle of the healthy side and preoperative carrying angle of the affected side, elbow flexion and extension range of motion, and lateral condylar prominence index (LCPI) showed no significant difference between the two groups ( P>0.05). The operation time, hospitalization cost, healing time of osteotomy, postoperative complications, and the carrying angle, LCPI, and elbow flexion and extention range of motion were recorded and compared between the two groups. The elbow function was assessed by Oppenheim score at 3 months after operation and at last follow-up. Results: The children in both groups were followed up 13-48 months, with an average of 26.7 months. There was 1 case of needle tract infection in the observation group and 2 cases in the control group, and no nerve injury occurred, the difference in the incidence of complication (5.88% vs 10.53%) between the two groups was not significant ( χ 2=0.502, P=0.593). There was no significant difference in the operation time and fracture healing time between the two groups ( P>0.05); the hospitalization cost of the observation group was significantly higher than that of the control group ( P<0.05). The Oppenheim score of the observation group was significantly better than that of the control group at 3 months after operation ( P<0.05), but there was no significant difference in the Oppenheim score between the two groups at last follow-up ( P>0.05). At last follow-up, the carrying angle of affected side significantly improved in both groups when compared with preoperative ones ( P<0.05); the differences of the pre- and post-operative carrying angle of affected side and elbow flexion and extension range of motion showed no significant differences between the two groups ( P>0.05), but the difference in pre- and post-operative LCPI of the observation group was significantly better than that of the control group ( P<0.05). Conclusion: External fixator combined with Kirschner wire fixation and Kirschner wire fixation both can achieve satisfactory correction of cubitus varus deformity in children, and the former can achieve better short-term functional recovery of elbow joint and reduce the incidence of humeral lateral condyle protrusion.

Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: A comprehensive analysis.

Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014-2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163-3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001-1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well-validated PH biomarkers, CA125 was still of prognostic value in the low-risk patients (HR: 1.014, 95% CI: 1.004-1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Lable-free aptamer portable colorimetric smartphone for gliadin detection in food.

For individuals with celiac disease (CD), the current clinical therapy option available is a lifelong gluten-free diet. Therefore, it is essential to swiftly and efficiently detect gluten in foods. A colorimetric sensor has been developed, which operates by regulating the aggregation and dispersion state of AuNPs induced by high concentration NaCl through the specific binding of gliadin and aptamer, thereby achieving rapid detection of gliadin in flour. It is found that the sensor exhibits good linearity in the concentration range of 0.67-10 µM and the LOD (3σ/S) is 12 nM. And it can accurately distinguish various types of free-gliadin samples, with a spiked recovery rate of 85%-122.3%. To make the detection process more convenient, the colorimetric results of the biosensor were translated into RGB color-gamut parameters by a smartphone color-picking program for further analysis. Gliadin can still be accurately quantified with the established smartphone platform, and a correlation coefficient of 0.988 was found. The proposed portable smartphone aptamer colorimetric sensing device has achieved satisfactory results in the rapid detection of gliadin in food.

Machine learning in RNA structure prediction: Advances and challenges.

RNA molecules play a crucial role in various biological processes, with their functionality closely tied to their structures. The remarkable advancements in machine learning techniques for protein structure prediction have shown promise in the field of RNA structure prediction. In this perspective, we discuss the advances and challenges encountered in constructing machine learning-based models for RNA structure prediction. We explore topics including model building strategies, specific challenges involved in predicting RNA secondary (2D) and tertiary (3D) structures, and approaches to these challenges. In addition, we highlight the advantages and challenges of constructing RNA language models. Given the rapid advances of machine learning techniques, we anticipate that machine learning-based models will serve as important tools for predicting RNA structures, thereby enriching our understanding of RNA structures and their corresponding functions.

Optimal short-term outcomes in balloon pulmonary angioplasty: the minimum frequency of three sessions annually.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. OBJECTIVES: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. DESIGN: Retrospective cohort. METHODS: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. RESULTS: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9-16, ⩾17) and T/P (⩽0.789, 0.790-1.263, ⩾1.264). CONCLUSION: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

The least number of BPA session to reach a favorable outcomeWhy was the study done? Balloon pulmonary angioplasty (BPA) has been recommended for patients with chronic thromboembolic pulmonary hypertension, which can significantly improve patients' hemodynamics. However, BPA is typically performed in a stepwise manner, and the duration from the initial session to the final session could extend over a year. If patients could not quickly undergo adequate number of BPA sessions and reach hemodynamic target due to various reasons, what is the best frequency of BPA for them? What did the researchers do? We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of BPA sessions, we divided patients into different groups to identify the best frequency of BPA to improve prognosis. What did the researchers find? Patients who received at least two BPA sessions within six months had significantly better prognosis than those with one BPA session. Patients who received at least three BPA sessions within a year had significantly better prognosis than those with two BPA sessions. What do the findings mean? To achieve optimal short-term outcome, patients might need to undergo at least two BPA sessions within six months, and undergo at least three BPA sessions within a year.

Role of the Systemic Inflammatory Response Index in Predicting Disease Severity and Prognosis in Idiopathic Pulmonary Arterial Hypertension.

Introduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH. Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration. Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073-1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society. Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.

Diagnostic Efficacy of High-frequency Ultrasound (HFU) in Early Diagnosis of Congenital Hip Dysplasia.

BACKGROUND: Hip dysplasia is one of the most prevalent disorders in children and one of the three primary congenital orthopedic deformities. Although there are numerous existing methods (e.g., CT, MRI and arthrography) for early identification of hip dysplasia, their diagnostic criteria differ widely. It is critical to establish a safe, accurate, and reliable way for early diagnosis and treatment of hip dysplasia. OBJECTIVE: This study aimed to analyze the diagnostic efficacy of high-frequency ultrasound (HFU) for congenital developmental hip dysplasia and hip dislocation and to provide a reference for the early diagnosis of congenital hip dysplasia in the future. METHODS: A total of 104 infants and children suspected of having congenital hip dislocation or developmental hip dysplasia admitted to our hospital from April 2019 to August 2022 were enrolled as study subjects. All the infants and children were subjected to HFU and X-ray examination in our hospital. The diagnostic efficacy of HFU for congenital hip dysplasia was observed using X-ray as the gold standard. RESULTS: HFU confirmed 79 cases of congenital hip dysplasia, while X-ray confirmed 71 cases. The sensitivity and specificity of HFU were 77.42% and 83.33%, respectively, in the diagnosis of congenital developmental hip dysplasia, 76.47% and 96.55% in the diagnosis of congenital hip dislocation, and 77.22% and 60% in the diagnosis of congenital hip abnormality, which is very close to the gold standard. According to statistics on infants and children, the majority of patients were girls, and the left joint was more likely to be affected. CONCLUSION: HFU has excellent diagnostic efficiency for congenital developmental hip dysplasia and hip dislocation, which can be considered an early assessment method for congenital hip dysplasia in the future.

A new technique of intramedullary elastic reduction of the "de-sharpened" Kirschner wire for the treatment of Gartland type III posterolateral displaced supracondylar fracture of the humerus in children.

OBJECTIVE: To compare the clinical effects of intramedullary elastic reduction of the "de-sharpened Kirschner wire and traditional three-dimensional manipulation in the treatment of Gartland type III posterolateral supracondylar fracture of the humerus in children. METHODS: A retrospective cohort analysis was made on 106 cases of Gartland type III posterolateral supracondylar fracture of the humerus treated in the Department of Orthopaedics of a Children's Hospital from March 2020 to March 2022. According to different surgical technology, the patients were divided into two groups: intramedullary elastic reduction of the de-sharpened Kirschner wire group (experimental group, n = 50) and traditional three-dimensional manipulation group (control group, n = 56). The surgical operating time, intraoperative fluoroscopy times, postoperative Baumann angle changes, postoperative elbow function Flynn score, and complications were collected and compared between the two groups. RESULTS: All the enrolled cases underwent surgery successfully and were followed-up at least 6 months. The surgical operating time of the experimental group was 32.88 ± 3.69 min and that of the control group was 45.56 ± 10.13 min, and the difference was statistically significant (P < 0.05). The intraoperative fluoroscopy times were 20.62 ± 5.41 times in the experimental group and 32.48 ± 8.20 times in the control group (P < 0.05). The change of Baumann angle in the experimental group after operation was 2.3 ± 1.3 and that in the control group was 6.0 ± 2.1 (P < 0.5). Elbow joint Flynn scoring standard to evaluate the curative effect: the excellent and good rate was 98.00% (49/50) in the experimental group and 92.86% (52/56) in the control group (P > 0.5). There were no complications such as osteomyelitis, compartment syndrome, iatrogenic vascular and nerve injury, and myositis ossificans in either group. CONCLUSIONS: Good functional outcome can be obtained with both intramedullary elastic reduction of the de-sharpened Kirschner wire and traditional three-dimensional manipulation for Gartland type III posterolateral displaced supracondylar fracture of the humerus in children; however, the former does not need repeated manipulation, and the operation time is shorter, the number of intraoperative fluoroscopy is less, and the recovery of the Baumann angle is better.

Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome.

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of ß3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Risk factor analysis of femoral avascular necrosis after operation for Tönnis grade IV developmental dysplasia of the hip.

PURPOSE: We explored the risk factors for avascular necrosis (AVN) after surgery using open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV developmental dysplasia of the hip (DDH). METHODS: In this retrospective study, we collected data of patients with Tönnis grade IV DDH treated with open reduction and pelvic osteotomy combined with femoral osteotomy from January 2012 to May 2020. The patients were divided into the AVN group and non-AVN group using the Kalamchi-MacEwen classification system. The clinical and imaging data of the two groups were collected, and the possible risk factors were included in the analysis. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors and odds ratios of AVN. RESULTS: In all, 254 patients (mean age; 2.6±0.9 years, 278 hips) were included. The mean follow-up time was 3.8±1.5 years. A total of 89 hips (32%) were finally classified as AVN (Kalamchi-MacEwen II-IV). Univariate analysis showed significant associations with AVN for age (p=0.006), preoperative femoral neck anteversion (FAV) (p<0.001), femoral osteotomy length to dislocation height ratio (FDR) <1 (p<0.001), and the epiphyseal ossific nucleus diameter to the neck diameter ratio (ENR) <50% (p=0.009). Multivariate logistic regression analysis showed that only excessive preoperative FAV (OR: 1.04; 95% CI: 1.02-1.05; p<0.001) and FDR<1 (OR: 3.58; 95% CI: 2.03-6.31; p<0.001) were independent risk factors for femoral head necrosis. CONCLUSION: Excessive preoperative FAV and FDR<1 are important risk factors for femoral AVN after open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV DDH. For children with DDH with high dislocation and excessive FAV, clinicians should fully evaluate their condition and design more personalized treatment programs to prevent AVN.

Sleep-disordered breathing patterns and prognosis in pulmonary arterial hypertension: A cluster analysis of nocturnal cardiorespiratory signals.

BACKGROUND: Sleep-disordered breathing (SDB) is common among pulmonary arterial hypertension (PAH) patients and has been associated with unfavorable outcomes. This study aims to cluster overnight cardiorespiratory signals to investigate PAH phenotypes and examining their prognostic implications. METHODS: In this retrospective cohort study, we recruited consecutive PAH patients who underwent right heart catheterization and nocturnal cardiorespiratory polygraphy to evaluate SDB. Cluster analysis was employed to classify patients based on their SDB patterns. Cox regression analysis and Kaplan-Meier curves were utilized to assess the association between cluster membership and clinical outcomes. Logistic regression was used to identify risk factors associated with the cluster at higher risk of adverse outcomes. RESULTS: The study comprised 386 PAH patients, with a mean age of 44.7 ± 17.0 years, of which 46.6 % were male. Three distinct clusters of PAH patients were identified: Cluster 1 (N = 182) presented with minimal SDB, Cluster 2 (N = 125) displayed obstructive sleep apnea (OSA) without significant hypoxemia, and Cluster 3 (N = 79) exhibited predominantly severe hypoxemic burden along with comorbid OSA. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95 % confidence interval [CI] 1.08-3.56, P = 0.027) compared to those in Clusters 1, even after adjusting for common confounders. The rate of clinical worsening for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 % vs. 12.6 % and 19.2 %, respectively, log-rank P = 0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95 % CI 1.00-1.02, P = 0.004). CONCLUSIONS: Patients with PAH who have nocturnal hypoxemia and OSA had worse clinical outcomes compared to those with only minimal SDB. Tailored management strategies that address both PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.

Angiographic classification of total occlusion and its implication on balloon pulmonary angioplasty.

AIMS: Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. METHODS AND RESULTS: All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed-head, round-head, and orifice occlusions. Pointed-head occlusion could be successfully addressed using soft-tip wire, round-head occlusion warranted hard-tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed-head (95.45%), round-head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round-head occlusion vs. pointed-head occlusion, OR 24.500, 95% CI 2.498-240.318, P = 0.006; orifice occlusion vs. pointed-head occlusion, OR 42.000, 95% CI 3.034-581.434, P = 0.005). CONCLUSIONS: Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

Kirschner wire reconstruction of medial and lateral column periosteal hinge in the treatment of multidirectionally unstable supracondylar fracture of the humerus in children.

AIM AND OBJECTIVE: To compare the clinical effect of reconstruction of internal and lateral column periosteal hinge-assisted treatment with Kirschner wire and internal fixation with Kirschner wire in the treatment of multidirectional unstable supracondylar fractures of humerus in children. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 48 patients (31 male, 17 female; mean age: 6.7 ± 2.4 years old) with multidirectionally unstable supracondylar fractures of the humerus treated in our Hospital from August 2020 to August 2022. Twenty-five cases were treated with Kirschner wire reconstruction of the internal and lateral column periosteal hinge assisted by closed reduction and Kirschner wire internal fixation (study group). Twenty-three cases were treated with closed reduction and Kirschner wire internal fixation (control group). The operation time, intraoperative fluoroscopy times, percentage of patients who underwent open reduction after failure of closed reduction, fracture healing time, Baumann angle (BA), shaft-condylar angle (SCA), range of motion (ROM), and Flynn score of elbow at the last follow-up were compared between two groups. Complications such as infection and irritation of Kirschner wire tail were observed in two groups 2 months after the operation. RESULTS: All patients were followed up for 10-22 months ([13.85 ± 2.89] months). The average operation time of the control group was 82.1 min, which was significantly longer than that of the study group 32.3 min (P < 0.05). The number of intraoperative fluoroscopy (29.4 ± 9.2) in the control group was significantly higher than that in the study group (15.2 ± 6.3) (P < 0.05). The incision rate of the control group was 17% while that of the study group was 0 (P < 0.05). According to Flynn score, the excellent and good rate of the elbow joint in the control group was 86.9% (20/23). The excellent and good rate of the elbow joint in the study group was 92.0% (23/25) (P > 0.05). There was no significant difference in fracture healing time, BA, SCA, and ROM between the two groups (P > 0.05). No infection or Kirschner wire tail irritation occurred in the two groups during the 2-month follow-up. CONCLUSION: Reconstruction of internal and lateral periosteal hinges with Kirscher wire has similar effects to closed reduction and Kirschner wire fixation in the treatment of multidirectionally unstable supracondylar fractures of the humerus in children, but it can shorten the operation time and reduce intraoperative fluoroscopy times and incision rate.

[Short-term effectiveness of ultrasound-guided Kirschner wire provocation technique in treatment of Salter-Harris types â and â ¡ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents].

Objective: To investigate the short-term effectiveness of ultrasound-guided closed reduction by Kirschner wire provocation technique in the treatment of Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents. Methods: Between May 2019 and May 2022, 41 patients with Salter Harris types Ⅰ and Ⅱ distal tibial epiphyseal fractures were admitted, all of whom had periosteal entrapment on preoperative MRI, and 38 cases (92.7%) were confirmed to have periosteal entrapment by intraoperative ultrasound. There were 24 males and 14 females, the age ranged from 6.8 to 15.7 years, with an average of 10.7 years; and there were 20 cases of Salter Harris type Ⅰ and 18 cases of type Ⅱ. The time from injury to operation was 22-76 hours, with an average of 28.4 hours. The preoperative imaging examination showed excellent alignment in 4 cases, good in 20 cases, and poor in 14 cases. The ultrasound guided Kirschner wire provocation technique for closed reduction and percutaneous Kirschner wire internal fixation were performed. The operation time, intraoperative fluoroscopy frequency, fracture healing time, and complications were recorded. Anteroposterior and lateral X-ray films of the affected ankle joint were taken before operation, at 3 months after operation, and at last follow-up to observe the healing of the fracture, and anteroposterior X-ray films of the whole length of both lower limbs were taken to evaluate the alignment of the force lines of the affected limbs. The range of motion (ROM), visual analogue scale (VAS) score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used to evaluate ankle function. The mechanical lateral distal tibia angle (mLDTA) and the anatomic anterior distal tibia angle (aADTA) were measured. Results: The operation time ranged from 17 to 52 minutes, with an average of 22.6 minutes, and the intraoperative fluoroscopy frequency ranged from 3 to 11 times, with an average of 4.2 times. X-ray examination during operation and at 2 days after operation showed that anatomical reduction was achieved. All patients were followed up 10-24 months, with an average of 16.4 months. All fractures healed in 6.1-7.2 weeks, with an average of 6.3 weeks; no fracture displacement occurred, and the patients recovered to their pre-injury level of motion at 6 months after operation. Needle tail irritation occurred in 2 cases at 4 weeks after operation, and they recovered after symptomatic treatment. During the follow-up, there was no serious complication such as incision deep infection, bone nonunion, delayed union, and malunion. At last follow-up, the patients' alignment were all excellent, and the difference was significant when compared with preoperative one ( Z=-7.471, P<0.001). The VAS score, AOFAS ankle-hindfoot score, dorsiflexion-plantar flexion ROM, varus-valgus ROM, mLDTA, and aADTA significantly improved at 3 months after operation and last follow-up when compared with preoperative ones ( P<0.05). Conclusion: Ultrasound-guided closed reduction by Kirschner wire provocation technique for treating Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents is minimally invasive and safe.