EGFR promotes ALKBH5 nuclear retention to attenuate N6-methyladenosine and protect against ferroptosis in glioblastoma.

Growth factor receptors rank among the most important oncogenic pathways, but pharmacologic inhibitors often demonstrate limited benefit as monotherapy. Here, we show that epidermal growth factor receptor (EGFR) signaling repressed N6-methyladenosine (m6A) levels in glioblastoma stem cells (GSCs), whereas genetic or pharmacologic EGFR targeting elevated m6A levels. Activated EGFR induced non-receptor tyrosine kinase SRC to phosphorylate the m6A demethylase, AlkB homolog 5 (ALKBH5), thereby inhibiting chromosomal maintenance 1 (CRM1)-mediated nuclear export of ALKBH5 to permit sustained mRNA m6A demethylation in the nucleus. ALKBH5 critically regulated ferroptosis through m6A modulation and YTH N6-methyladenosine RNA binding protein (YTHDF2)-mediated decay of the glutamate-cysteine ligase modifier subunit (GCLM). Pharmacologic targeting of ALKBH5 augmented the anti-tumor efficacy of EGFR and GCLM inhibitors, supporting an EGFR-ALKBH5-GCLM oncogenic axis. Collectively, EGFR reprograms the epitranscriptomic landscape through nuclear retention of the ALKBH5 demethylase to protect against ferroptosis, offering therapeutic paradigms for the treatment of lethal cancers.

Recent Advances in Palladium-Catalyzed Asymmetric Heck/Tsuji-Trost Reactions of 1,n-Dienes.

Transition-metal catalyzed tandem asymmetric reactions were powerful tools to access various chiral compounds. Many strategies have been developed for the coupling of 1,n-dienes with aryl halides via a tandem Heck/Tsuji-Trost process. However, the control of regio- and stereo-chemistry remains a challenging task. This minireview details the recent advances in the field of asymmetric Heck/Tsuji-Trost reactions catalyzed by palladium complex, which have opened new opportunities and expanded our understanding in this area of research in recent years.

Recyclable N-Heterocyclic Carbene Porous Coordination Polymers with Two Distinct Metal Sites for Transformation of CO2 to Cyclic Carbonates.

Single-component catalysts with integrated multiple reactive centers could work in concert to achieve enhanced activity tailored for specific catalytic reactions, but they remain underdeveloped. Herein, we report the construction of heterogeneous bimetallic porous coordination polymers (PCPs) containing both porphyrin and N-heterocyclic carbene (NHC) metal sites via the coordinative assembly of the NHC functionalities. Three heterobimetallic PCPs (TIPP-Zn-Pd, TIPP-Cu-Pd and TIPP-Ni-Pd) have been prepared to verify this facile synthetic strategy for the first time. In order to establish a cooperative action toward the catalytic CO2 cycloaddition with epoxides, an additional tetraalkylammonium bromide functionality has also been incorporated into these polymeric structures through the N-substituent of the NHC moieties. The resulting heterogeneous bimetallic catalyst TIPP-Zn-Pd exhibits the best catalytic performance in CO2 cycloaddition with styrene oxide (SO) under solvent-free conditions at atmospheric pressure and is applicable to a wide range of epoxides. More importantly, TIPP-Zn-Pd works smoothly and is recyclable in the absence of a cocatalyst under 1.0 MPa of CO2 at 60 °C. This indicates that TIPP-Zn-Pd is quite competitive with the reported heterogeneous catalysts, which typically require a high reaction temperature above 100 °C under cocatalyst-free conditions. Thus, this work provides a new approach to design heterogeneous bimetallic PCP catalysts for high-performance CO2 fixation under mild reaction conditions.

Endovascular Denervation for the Improvement of Limb Ischemia in Patients with Peripheral Artery Disease: A Randomized Clinical Trial.

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.

Risk Factors for Access-Related Adverse Events Related to the Preclose Technique in Thoracic Endovascular Aortic Repair.

PURPOSE: To analyze the risk factors for access-related adverse events (AEs) of the preclose technique in thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Ninety-one patients with Stanford type B aortic dissection who underwent the preclose technique in TEVAR between January 2013 and December 2021 were included. According to the occurrence of access-related AEs, the patients were divided into 2 groups: those with AE and those without AE. Age, sex, combined diseases, body mass index, skin depth, femoral artery diameter, access calcification, iliofemoral artery tortuosity, and sheath size were recorded for risk factor analysis. The sheath-to-femoral artery ratio (SFAR), the ratio of the femoral artery inner diameter (in millimeters) to the sheath's outer diameter (in millimeters), was also included in the analysis. RESULTS: SFAR was identified as an independent risk factor for AEs using multivariable logistic analysis (odds ratio, 251.748; 95% CI, 7.004-9,048.534; P = .002). The cutoff value of SFAR was 0.85 and was related to a higher incidence of access-related AEs (5.2% vs 33.3%, P = .001), especially to a higher stenosis rate (0.0% vs 21.2%, P = .001). CONCLUSIONS: SFAR is an independent risk factor for access-related AEs of preclose in TEVAR with a cutoff value of 0.85. SFAR could be a new criterion for preoperative access evaluation in high-risk patients that may allow the detection and treatment of access-related AEs at the early stage.

Placement of Bare Self-Expanding Metal Stent for Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: To evaluate the safety and efficacy of placing bare self-expanding metal stent (SEMS) for treating isolated superior mesenteric artery dissection (ISMAD). METHOD: Patients with ISMAD who received bare SEMS from January 2014 to December 2021 at the authors' center were included. Baseline characteristics, clinical manifestation, radiological findings, and treatment outcomes, including symptom relief and SMA remodeling, were analyzed. RESULT: A total of 26 patients were included in this study. Among the patients, 25 were admitted due to persistent abdominal pain, and 1 was admitted based on computed tomography angiography (CTA) during physical examination. According to CTA scan, the percentage of stenosis was 91% (53.8-100%), and the length of dissection was 100.2 ± 8.4 mm. All patients received bare SEMS placement. The median time to symptom relief was 1 day (interquartile range, 1 3 days). The the median follow-up time of CTA was 6.8 months (range, 2-85 months), with an average of 16.2 months. Complete remodeling of the superior mesenteric artery (SMA) was recorded in 24 patients. The median time to remodeling was 3 months with an average of 4.7 months. Survival analysis indicated no significance difference in remodeling time between different ISMAD types based on Yun classification (P = 0.888) or between acute and nonacute disease (P = 0.423). Incomplete remodeling was noted in 2 patients. Distal stent occlusion without SMA-related symptoms was seen in 1 patient. Proximal stent stenosis occurred in 1 patient, and restenting was performed. The median follow-up time by telephone was 20.8 (4-91.5) months, and no intestinal ischemic symptoms were observed in any patient. CONCLUSIONS: Bare SEMS placement can effectively relieve SMA-related symptoms in a short time and promote dissection remodeling in ISMAD. Time from symptom onset and classification of ISMAD seem not to have effects on SMA remodeling after bare SEMS placement.

Pd/Ming-Phos-Catalyzed Asymmetric Three-Component Arylsilylation of N-Sulfonylhydrazones: Enantioselective Synthesis of gem-Diarylmethine Silanes.

A Pd-catalyzed enantioselective three-component reaction of N-sulfonylhydrazones, aryl bromides, and silylboronic esters is developed, enabling the synthesis of chiral gem-diarylmethine silanes in high enantioselectivity with the use of a newly identified Ming-Phos. Compared with N-tosyl, the more easily decomposed N-mesitylsulfonyl is more suitable as the masking group of electron-rich hydrazone to improve the reaction efficiency. The reaction features a broad scope concerning both coupling partners, high enantioselectivity, and mild reaction conditions. The ready access to enantiomers and utility of this catalytic method are also presented.

Low-Temperature Light-off MnOx -Na2 WO4 -Based Catalysts: A Step Forward to OCM Process Industrialization.

Oxidative coupling of methane (OCM) catalyzed by MnOx -Na2 WO4 -based catalysts has great industrial potential to convert CH4 directly to C2-3 products, but the high light-off temperature is a big challenge to OCM commercialization. The reaction mechanism studies disclosed that O2 /CH4 -activation relevant "Mn2+ ↔Mn3+ " redox cycle is tightly linked with the catalyst light-off. One concept is thus put forward that the OCM light-off temperature could be lowered once a "Mn2+ ↔Mn3+ " redox cycle was established to be triggered at low temperature over MnOx -Na2 WO4 -based catalysts. The relevant studies in recent years are reviewed, showing that the establishment of low-temperature light-off "Mn2+ ↔Mn3+ " redox cycle over the MnOx -Na2 WO4 -based catalysts indeed works effectively toward a low-temperature light-off OCM process. Moreover, three perspectives for the OCM industrialization are discussed based on this concept, including monolithic catalyst, fluidized-bed method and chemical-looping process.

Enhanced catalytic reduction of p-nitrophenol and azo dyes on copper hexacyanoferrate nanospheres decorated copper foams.

Catalytic reduction of nitroaromatic compounds using low-cost non-precious metal containing catalyst remains an essential topic in wastewater treatment. Herein, copper hexacyanoferrate nanospheres decorated copper foams (CF) were prepared by a facile method, and it was used as structured catalysts for the reduction of p-nitrophenol (p-NP) and azo dyes. The catalyst obtained by calcination at 200 °C shows the highest catalytic activity, with an almost complete reduction of p-NP within 3 min with a rate of 2.057 min-1 at room temperature, and it exhibited excellent reusability in successive 6 cycles. The effects of temperature, initial concentration, pH, and flow rate on p-NP reduction were investigated. Moreover, the mechanistic investigation revealed that fast electron transfer ability and enhanced adsorption for p-NP contributed to its enhanced catalytic performances. This work put forward an efficient approach for the construction of structured catalysts with enhanced performance in catalytic reduction applications.

Oxidative Coupling of Methane: Examining the Inactivity of the MnOx -Na2 WO4 /SiO2 Catalyst at Low Temperature.

Oxidative coupling of methane (OCM) catalyzed by MnOx -Na2 WO4 /SiO2 has great industrial promise to convert methane directly to C2-3 products, but its high light-off temperature is the most challenging obstacle to commercialization and its working mechanism is still a mystery. We report the discovery of a low-temperature active and selective MnOx -Na2 WO4 /SiO2 catalyst enriched with Q2 units in the SiO2 carrier, being capable of converting 23 % CH4 with 72 % C2-3 selectivity at 660 °C. From experiments and theoretical calculations, a large number of Q2 units in the MnOx -Na2 WO4 /SiO2 catalyst is a trigger for markedly lowering the light-off temperature of the Mn3+ ↔Mn2+ redox cycle involved in the OCM reaction because of the easy formation of MnSiO3 . Notably, the MnSiO3 formation proceeds merely through the SiO2 -involved reaction in the presence of Na2 WO4 : Mn7 SiO12 +6 SiO2 ↔7 MnSiO3 +1.5 O2 . The Na2 WO4 not only drives the light-off of this cycle but also gets it working with substantial selectivity toward C2-3 products. Our findings shine a light on the rational design of more advanced MnOx -Na2 WO4 based OCM catalysts through establishing new Mn3+ ↔Mn2+ redox cycles with lowered light-off temperature.

Electronically Engineering Water Resistance in Methane Combustion with an Atomically Dispersed Tungsten on PdO Catalyst.

Improving the low-temperature water-resistance of methane combustion catalysts is of importance for industrial applications and it is challenging. A stepwise strategy is presented for the preparation of atomically dispersed tungsten species at the catalytically active site (Pd nanoparticles). After an activation process, a Pd-O-W1 -like nanocompound is formed on the PdO surface with an atomic scale interface. The resulting supported catalyst has much better water resistance than the conventional catalysts for methane combustion. The integrated characterization results confirm that catalytic combustion of methane involves water, proceeding via a hydroperoxyl-promoted reaction mechanism on the catalyst surface. The results of density functional theory calculations indicate an upshift of the d-band center of palladium caused by electron transfer from atomically dispersed tungsten, which greatly facilitates the adsorption and activation of oxygen on the catalyst.

Pd/GF-Phos-Catalyzed Asymmetric Three-Component Coupling Reaction to Access Chiral Diarylmethyl Alkynes.

Significant attention has been given in the past few years to the selective transformations of N-tosylhydrazones to various useful compounds. However, the development of enantioselective versions poses considerable challenges. Herein we report a Pd-catalyzed enantioselective three-component coupling of N-tosylhydrazone, aryl halide, and terminal alkyne under mild conditions utilizing a novel chiral sulfinamide phosphine ligand (GF-Phos), which provides a facile access to chiral diarylmethyl alkynes, which are useful synthons in organic synthesis as well as exist as the skeleton in many bioactive molecules. A pair of enantiomers of the product could be easily prepared using the same chiral ligand by simply changing the aryl substituents of the N-tosylhydrazone and aryl halide. The salient features of this reaction include the readily available starting materials, general substrate scope, high enantioselectivity, ease of scale-up, mild reaction conditions, and versatile transformations.

A General Strategy for Fabricating Isolated Single Metal Atomic Site Catalysts in Y Zeolite.

Exploring high-performance zeolite-supported metal catalysts is of great significance. Herein, we develop a strategy for fabricating isolated single metal atomic site catalysts in Y zeolite (M-ISAS@Y, M = Pt, Pd, Ru, Rh, Co, Ni, Cu) by in situ separating and confining a metal-ethanediamine complex into ß-cages during the crystallization process followed by thermal treatment. The M-ISAS are stabilized by skeletal oxygens of Y zeolite, and the crystallinity, porosity, and large surface area are well inherited in M-ISAS@Y. As a demonstration, acidic Pt-ISAS@Y is used for n-hexane isomerization involving consecutive catalytic dehydrogenation/hydrogenation on Pt-ISAS and isomerization on Brønsted acid sites. The turnover frequency value of Pt-ISAS reaches 727 h-1, 5 times more than Pt nanoparticles (∼3.5 nm), with a total isomer selectivity of more than 98%. This strategy provides a convenient route to fabricate promising zeolite-based M-ISAS catalysts for industrial applications.

Soluble galectin 9 potently enhanced regulatory T-cell formation, a pathway impaired in patients with intracranial aneurysm.

Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal-9), the natural ligand of Tim-3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal-9 was primarily expressed by CD4+ CD25- T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4+ CD25+ Treg cells. In IA patients, the Gal-9 expression was significantly lower than in healthy controls. CD4+ CD25- Tconv cells could be induced into Foxp3-expressing induced Treg (iTreg) cells using a TGF-ß-containing milieu. We found that soluble Gal-9 significantly enhanced this process by potently upregulating the expression of Foxp3, IL-10 and TGF-ß in a concentration-dependent manner. In addition, in the absence of additional Gal-9, the level of Foxp3 upregulation was directly correlated with the level of intrinsic Gal-9 expression. Notably, the strength of external Gal-9-mediated effects was significantly lower in IA patients than in healthy controls. Using a Tim-3 blocking antibody, we found that the promotion of iTreg development by soluble Gal-9 was dependent on the Tim-3 signalling pathway. Overall, our investigations demonstrated that Gal-9 presented a critical role in the development of iTreg cells. However, this mechanism was impaired in IA patients due to lower expression of both Gal-9 and Tim-3.

[Risk factors for primary patency of occlusive femoral artery after subintimal angioplasty in diabetics].

OBJECTIVE: To retrospectively explore the status of primary patency after subintimal angioplasty (SIA) and identify the risk factors affecting for primary patency of occlusive lesions in femoral arteries after SIA in patients with diabeticses mellitus. METHODS: From January 2009 to May 2011, 43 diabetics patients with 43 occlusive femoral arteries were successfully underwent subintimal angioplasty successfully with or without stenting.Recurrent stenosis was defined as an arterial diameter reduction of over 50%. And arterial occlusion was confirmed by an absence of color or power signal in the arterial lumen measured on color Doppler. The Kaplan-Meier method was employed to determine the primary patency. A multivariate analysis was performed with Cox's proportional hazard regression model to determine the independent factors for effects on primary patency. RESULTS: A total of 17 morphologic abnormalities occurred during a median follow-up period of 21 (14-32) months. The median follow time of the successful 43 patients was 21 months (from 14 to 32 month). Minor complications occurred in 4 patents. There was no early mortality. A total of 17 morphologic abnormalities occurred during follow-up. The cumulative primary patency at 6, 12, 12 and 24 months were (86 ± 5)%, (75% ± 7)% and (43 ± 12)% respectively. Primary patency was affected negatively by the number of occlusive run-off vessels (B = -4.417, SX- = 1.627, P = 0.007) and the severity degree according to the Inter-society consensus for the management of peripheral arterial disease (TASC II) classification (B = -2.502, SX- = 0.955, P = 0.009), and positively by the a history of smoking (B = 3.115, SX- = 1.523, P = 0.041). CONCLUSIONS: Subintimal angioplasty is a less invasive procedure with a lower rate of morbidity and adequate cceptable patency. And the number of occlusive run-off vessels, lesion typing degree of severity according to the TASC II classification negatively and smoking positively have significant influence effects on the primary patency in diabetics patients.

Synergistic effect between In2O3 and ZrO2 in the reverse water gas shift reaction.

Efficient activation of CO2 at low temperature was achieved through the interface effect between In2O3 and ZrO2 by their geometric and electronic effects. The results show that 75In2O3-25ZrO2 (In2O3 : ZrO2 molar ratio of 3 : 1), as a catalyst for the reverse water gas shift reaction, can achieve 28% CO2 conversion with 96% CO selectivity at 400 °C, 0.1 MPa, a H2 : CO2 molar ratio of 3 : 1 and a gas hourly space velocity of 10 000 mL g-1 h-1. In situ FTIR experiments provide a basis for clarifying the pivotal role of formate (facilitated at In2O3-ZrO2 interface) in this reaction.

Linking the Doping-Induced Trap States to the Concentration of Surface-Reaching Photoexcited Holes in Transition-Metal-Doped TiO2 Nanoparticles.

Transition-metal doping has been demonstrated to be effective for tuning the photocatalytic activity of semiconductors. Nonetheless, the impact of doping-induced trap states on the concentration of surface-reaching photoexcited charges remains a topic of debate. In this study, through time-resolved spectroscopies and kinetic analysis, we found that the concentration of surface-reaching photoholes (Ch+(surf)) in doped TiO2 nanoparticles sensitively relies on the type of dopants and their associated trap states. Among the studied dopants (Fe, Cu, and Co), Fe doping resulted in the most significant increase in Ch+(surf), nearly double that of Co or Cu doping. Fe-doping induced more effective hole trap states, acting as the mediator for interfacial charge transfer, thus accelerating charge separation and consequently enriching Ch+(surf). This work provides valuable insight into understanding and controlling Ch+(surf) in transition-metal-doped TiO2 materials.

Low-Temperature Synthesis of Cyano-Rich Modified Surface-Alkalinized Heterojunctions with Directional Charge Transfer for Photocatalytic In Situ Generation and Consumption of Peroxides.

The synthesis of low-temperature poly(heptazine imide) (PHI) presents a significant challenge. In this context, we have developed a novel low-temperature synthesis strategy for PHI in this work. This strategy involves the introduction of Na+ ions, which etch and disrupt the conjugated structure of carbon nitride (CN) during assisted thermal condensation. This disruption leads to the partial decomposition of the heptazine ring structure, resulting in the formation of C≡N functionalities on the CN surface, which are enriched with hydroxyl groups and undergo cyano modification. The formation of heterojunctions between CN and ZnO, which facilitate charge transfer along an immobilization pathway, accelerated charge transfer processes and improved reactant adsorption as well as electron utilization efficiency. The resulting catalyst was employed for the room temperature, atmospheric pressure, and solvent-free photocatalytic selective oxidation of cumene (CM), achieving a cumene conversion rate of 28.7% and a remarkable selectivity of 92.0% toward the desired product, cumene hydroperoxide (CHP). Furthermore, this CHP induced oxidative reactions, as demonstrated by the successful oxidation of benzylamine to imine and the oxidation of sulfide to sulfoxide, both yielding high product yields. Additionally, the utilization of a continuous-flow device significantly reduces the reaction time required for these oxidation processes. This work not only introduces an innovative approach to environmentally friendly, sustainable, clean, and efficient PHI synthesis but also underscores the promising potential and advantages of carbon nitride-based photocatalysts in the realm of sustainable and green organic transformations.

Gene Amplification of Mediator Subunit 30 Redirects the MYC Transcriptional Program and Oncogenesis.

Understanding the molecular mechanisms underlying tumorigenesis is crucial for developing effective cancer therapies. Here, we investigate the co-amplification of MED30 and MYC across diverse cancer types and its impact on oncogenic transcriptional programs. Transcriptional profiling of MYC and MED30 single or both overexpression/amplification revealed the over amount of MED30 lead MYC to a new transcriptional program that associate with poor prognosis. Mechanistically, MED30 overexpression/amplification recruits other Mediator components and binding of MYC to a small subset of novel genomic regulatory sites, changing the epigenetic marks and inducing the formation of new enhancers, which drive the expression of target genes crucial for cancer progression. In vivo studies in pancreatic ductal adenocarcinoma (PDAC) further validate the oncogenic potential of MED30, as its overexpression promotes tumor growth and can be attenuated by knockdown of MYC. Using another cancer type as an example, MED30 knockdown reduces tumor growth particularly in MYC high-expressed glioblastoma (GBM) cell lines. Overall, our study elucidates the critical role of MED30 overexpression in orchestrating oncogenic transcriptional programs and highlights its potential as a therapeutic target for MYC-amplified cancer.

Influence of kyphosis in ankylosing spondylitis on cardiopulmonary functions.

This paper aims at analyzing the characteristics of cardiopulmonary functions in the patients with ankylosing spondylitis (AS), and exploring the influence of global kyphosis (GK) on cardiopulmonary functions. Clinical data of 46 patients with AS and kyphosis, who had been admitted in our hospital from October 2021 to October 2022, were analyzed retrospectively. According to the to global kyphosis (GK) angle, 23 subjects were divided into Severe Group (GK > 95°), and 23 subjects were divided into in the Moderate Group (80°â€…≤ GK ≤ 95°). Cardiac structure and cardiopulmonary function parameters were compared between both groups, and the influences of GK Angle on other parameters were analyzed by Pearson or Spearman correlation analysis. The cardiac structure and function measurements in both groups were within the normal range. The pulmonary functions of both groups decreased to different extents. Correlation analysis showed that GK Angle was significantly negatively correlated with the left atrioventricular size (LAD, LVDD, LVSD) and diastolic function parameters (E/A, e'/a') in the patients with AS (P < .05); GK Angle was negatively correlated with restrictive ventilation parameters in the patients with AS (P < .05). The GK Angle of the patients with AS affects the cardiac structure and diastolic function. The larger the GK Angle is, the smaller the left and right at ventricle diameters are. In addition, GK Angle also affects the left ventricular diastolic function. GK Angle is related to the degree of pulmonary function impairment, and the larger the GK Angle is, the worse the pulmonary function it will be.