BackgroundCystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk.ObjectiveThe aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH).MethodWe retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization.ResultsA total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P < 0.001), mixed venous oxygen saturation (r = -0.216, P < 0.001), and tricuspid annular plane systolic excursion (r = -0.236, P < 0.001), and high cystatin C levels independently predicted a poor prognosis after adjusting potential confounders in different models (all P < 0.05). A three-group non-invasive risk model was constructed based on the combined assessment of the cystatin C and WHO-FC using dichotomous cut-off value. Those patients with higher cystatin C (≥ 1.0 mg/L) and a worse WHO-FC experienced the highest risk of endpoint occurrence. The predictive capacity of this model was comparable to that of an existing invasive risk stratification model (area under curve: 0.657 vs 0.643, P = 0.619).ConclusionsCystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.

IntroductionThis retrospective cohort study aimed to compare the change in upper airway and craniocervical posture after orthodontic treatment between adolescent and adult patients with Class II high-angle malocclusion.MethodsA total of 12 adolescent (mean ± standard deviation age = 13.0 ± 2.0 years) and 12 adult patients with Class II high-angle malocclusion (mean ± standard deviation age = 23.7 ± 6.4 years) were selected in this study. The lateral cephalograms and cone beam computed tomography images of adolescent and adult patients were taken before and after treatment, which can be employed to evaluate the variables of craniofacial morphology, upper airway, and craniocervical posture through paired t tests, respectively. An independent sample t test was performed to observe the differences between two groups after orthodontic intervention. For adults and adolescents, the correlation between craniofacial morphology, upper airway, and craniocervical posture was determined through Pearson correlation analysis.ResultsIn all subjects, the improvements in vertical and sagittal facial morphology after treatment were observed. Anterior and inferior movements of the hyoid bone, an increase of upper airway dimension, posterior tipping of the head and a reduction of cervical inclination in the lower and middle segments post-treatment were identified in adolescence (P < 0.05). Adults displayed anterior movements of the hyoid bone, whereas no significant difference was observed in upper airway dimension and craniocervical posture (P < 0.05). Notable differences were identified in the change of hyoid position and airway volume between two groups (P > 0.05). Mandibular plane inclination, growth pattern, occlusal plane inclination, and chin position were all significantly correlated with craniocervical posture in adolescent patients. Besides, the mandibular growth pattern and chin position in adult patients were significantly correlated with craniocervical posture (P < 0.05).ConclusionsOrthodontic treatment is capable of enhancing the facial profile of patients with skeletal class II high-angle while improving their upper airway morphology and craniocervical posture, where adolescents and adults differ substantially in that the former exhibit a more favorable alteration in the airway-craniocervical functional environment.

BackgroundToripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT 03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required.MethodsA partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental cost-effectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model.ResultsIn the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel.ConclusionAt a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China.

Sepsis-induced acute kidney injury (SI-AKI), a common critically ill, represents one of the leading causes of global death. Emerging evidence reveals autophagy as a pivotal modulator of SI-AKI. Autophagy affects the cellular processes of renal lesions, including cell death, inflammation, and immune responses. Herein, we conducted a systematic and comprehensive review on the topic of the proposed roles of autophagy in SI-AKI. Forty-one relevant studies were finally included and further summarized and analyzed. This review revealed that a majority of included studies (24/41, 58.5%) showed an elevation of the autophagy level during SI-AKI, while 22% and 19.5% of the included studies reported an inhibition and an elevation at the early stage but a declination of renal autophagy in SI-AKI, respectively. Multiple intracellular signaling molecules and pathways targeting autophagy (e.g. mTOR, non-coding RNA, Sirtuins family, mitophagy, AMPK, ROS, NF-Kb, and Parkin) involved in the process of SI-AKI, exerting multiple biological effects on the kidney. Multiple treatment modalities (e.g. small molecule inhibitors, temsirolimus, rapamycin, polydatin, ascorbate, recombinant human erythropoietin, stem cells, Procyanidin B2, and dexmedetomidine) have been found to improve renal function, which may be attributed to the elevation of the autophagy level in SI-AKI. Though the exact roles of autophagy in SI-AKI have not been well elucidated, it may be implicated in preventing SI-AKI through various molecular pathways. Targeting the autophagy-associated proteins and pathways may hint towards a new prospective in the treatment of critically ill patients with SI-AKI, but more preclinical studies are still warranted to validate this hypothesis.

BackgroundAnti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated.ObjectivesThe purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity.ResultsA total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed.ConclusionsAnti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

Pancreatic cancer is one of the most dangerous types of cancer today, notable for its low survival rate and fibrosis. Deciphering the cellular composition and intercellular interactions in the tumor microenvironment (TME) is a necessary prerequisite to combat pancreatic cancer with precision. Cancer-associated fibroblasts (CAFs), as major producers of extracellular matrix (ECM), play a key role in tumor progression. CAFs display significant heterogeneity and perform different roles in tumor progression. Tumor cells turn CAFs into their slaves by inducing their metabolic dysregulation, exacerbating fibrosis to acquire drug resistance and immune evasion. This article reviews the impact of metabolic reprogramming, effect of obesity and cellular crosstalk of CAFs and tumor cells on fibrosis and describes relevant therapies targeting the metabolic reprogramming.