A Chinese Multi-Specialty Delphi Consensus to Optimize RAASi Usage and Hyperkalaemia Management in Patients with Chronic Kidney Disease and Heart Failure.

Objective: Variations are present in common clinical practices regarding best practice in managing hyperkalaemia (HK), there is therefore a need to establish a multi-specialty approach to optimal renin-angiotensin-aldosterone system inhibitors (RAASi) usage and HK management in patients with chronic kidney disease (CKD) & heart failure (HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and how to manage HK in patients with CKD and HF.Methods: A steering expert group of cardiology and nephrology experts from across China convened to discuss challenges to HK management through a nominal group technique (NGT). The group then created a list of 41 statements for a consensus questionnaire, which was distributed for a further survey of in extended panel group of cardiologists and nephrologists across China. Consensus was assessed using a modified Delphi technique, with agreement defined as "strong" (≥75% and <90%) and "very strong" (≥90%). The steering group, data collection, and analysis were aided by an independent facilitator. Results: A total of 150 responses from 21 provinces across China were recruited in the survey. Respondents were comprised of an even split (n=75, 50%) between cardiologists and nephrologists. All 41 statements achieved the 75% consensus agreement threshold, of which 27 statements attained very strong consensus (≥90% agreement) and 14 attained strong consensus (agreement between 75% and 90%). Conclusions: Based on the agreement levels from respondents, the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.

The prognosis and management of reclassified systemic lupus erythematosus associated pulmonary arterial hypertension according to 2022 ESC/ERS guidelines.

BACKGROUND AND AIMS: The 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guideline has recently revised the hemodynamic definition of pulmonary arterial hypertension. However, there is currently limited research on the prognosis and treatment of system lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) patients that have been reclassified by the new hemodynamic definition. This study aims to analyze the prognosis of newly reclassified SLE-PAH patients and provide recommendations for the management strategy. METHODS: This retrospective study analyzed records of 236 SLE-PAH patients who visited Peking Union Medical College Hospital (PUMCH) from 2011 to 2023, among whom 22 patients were reclassified into mild SLE-PAH (mean pulmonary arterial pressure (mPAP) of 21-24 mmHg, pulmonary vascular resistance (PVR) of 2-3 WU, and PAWP ≤ 15 mmHg) according to the guidelines and 14 were defined as unclassified SLE-PAH patients (mPAP 21-24 mmHg and PVR ≤ 2 WU). The prognosis was compared among mild SLE-PAH, unclassified SLE-PH, and conventional SLE-PAH patients (mPAP ≥ 25 mmHg and PVR > 3WU). Besides, the effectiveness of pulmonary arterial hypertension (PAH)-specific therapy was evaluated in mild SLE-PAH patients. RESULTS: Those mild SLE-PAH patients had significantly longer progression-free time than the conventional SLE-PAH patients. Among the mild SLE-PAH patients, 4 did not receive PAH-specific therapy and had a similar prognosis as patients not receiving specific therapy. CONCLUSIONS: This study supports the revised hemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those mild and unclassified SLE-PH patients had a better prognosis, demonstrating the possibility and significance of early diagnosis and intervention for SLE-PAH. This study also proposed a hypothesis that IIT against SLE might be sufficient for those reclassified SLE-PAH patients.

Efficacy and safety of daratumumab plus bortezomib and dexamethasone in newly diagnosed Mayo 2004 stage IIIA or IIIB light-chain amyloidosis: a prospective phase II study.

Not available.

Identification and validation of the association of Janus kinase 2 mutations with the response to immune checkpoint inhibitor therapy.

BACKGROUND: Janus kinase 2 (JAK2) mutation plays an important role in T cell immunity. However, the effect of JAK2 mutation on immunotherapy is largely uncharacterized. METHODS: In this study, we analyzed the effect of JAK2 mutation on the efficacy and outcomes of immune checkpoint inhibitor (ICI) therapy in the discovery cohort (n = 662) and the verification cohort (n = 1423). Furthermore, we explored the association of JAK2 mutation with the tumor immune microenvironment in a multiomics cohort. RESULTS: In the discovery cohort (n = 662), JAK2 mutant-type patients had a better objective response rate (58.8% vs. 26.7%, P = 0.010), durable clinical benefit (64.7% vs. 38.9%, P = 0.043), progression-free survival (hazard ratio [HR] = 0.431, P = 0.015), and overall survival (HR = 0.378, P = 0.025), relative to JAK2 wild-type patients. Moreover, we further verified the prognostic significance of JAK2 mutation in an independent ICI treatment cohort with a larger sample size (n = 1423). In addition, we discovered that the JAK2 mutation was remarkably related to increased immunogenicity, such as a higher TMB, higher expression of costimulatory molecules and stimulation of antigen processing mechanisms. In addition, JAK2 mutation was positively correlated with activated anticancer immunity, such as infiltration of various immune cells and higher expression of chemokines. CONCLUSION: Our study demonstrates that JAK2 mutation is a novel marker that can be used to effectively predict prognosis and response to ICI therapy.

A novel method to quantify chitosan in aqueous solutions by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

In this study, a novel and accurate quantitative analysis method for the direct determination of chitosan (CS) in aqueous solutions using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is presented. By detecting the mass spectrum response intensity of a series of CS characteristic ion pairs, the sample concentration (abscissa) was linearly fitted with the total ion current (TIC) response intensity of its characteristic ion pairs (ordinate). A reliable standard curve was derived for quantifying CS in the range of 125-4000 ng/mL. Under the detection conditions, this CS quantification method yielded acceptable specificity (no interference peak), linearity (with correlation coefficient (r2) values >0.999), precision (acceptable limit RSDr < 3 %, RSDR < 6 %), accuracy (RE within the acceptable limits of ±5 %), and stability (acceptable limit RE within ±5 %, RSDr < 3 %). Moreover, the applicability of measurement was verified when a series of substrates did not interact with CS in the solution. Results have verified the applicability of this method for determining CS content in different composites. This study provides a method for determining CS content with significant practical value and economic benefit.

Restoration of autophagy activity by dipsacoside B alleviates exhaustive exercise-induced kidney injury via the AMPK/mTOR pathway.

Exhaustive exercise (EE) induces kidney injury, but its concrete mechanism has not been fully elucidated. Hepatoprotective effects of dipsacoside B (DB) have been found previously, involving in autophagy induction. However, whether DB exerts renal protective effect and its potential mechanism are still unknown. The present study aimed to investigate the benefit of DB in EE-induced kidney injury and decipher its underlying mechanism. Here, we found that DB ameliorated EE-induced renal dysfunction and renal histopathological injury in rats. DB possessed anti-inflammatory, anti-oxidative, and anti-apoptotic functions in kidneys of exercise-induced exhausted rats. Besides, DB improved autophagy function in kidneys of EE rats. Mechanically, activation of the adenylate-activating protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was implicated in the kidney injury-relieving effects and autophagy restoration induced by DB. Collectively, these findings provide reference for the clinical application of DB in preventing and managing EE-induced kidney injury.

Drug Repositioning for Amyloid Transthyretin Amyloidosis by Interactome Network Corrected by Graph Neural Networks and Transcriptome Analysis.

Amyloid transthyretin (ATTR) amyloidosis caused by transthyretin misfolded into amyloid deposits in nerve and heart is a progressive rare disease. The unknown pathogenesis and the lack of therapy make the 5-year survival prognosis extremely poor. Currently available ATTR drugs can only relieve symptoms and slow down progression, but no drug has demonstrated curable effect for this disease. The growing volume of pharmacological data and large-scale genome and transcriptome data bring new opportunities to find potential new ATTR drugs through computational drug repositioning. We collected the ATTR-related in the disease pathogenesis and differentially expressed (DE) genes from five public databases and Gene Expression Omnibus expression profiles, respectively, then screened drug candidates by a corrected protein-protein network analysis of the ATTR-related genes as well as the drug targets from DrugBank database, and then filtered the drug candidates on the basis of gene expression data perturbed by compounds. We collected 139 and 56 ATTR-related genes from five public databases and transcriptome data, respectively, and performed functional enrichment analysis. We screened out 355 drug candidates based on the proximity to ATTR-related genes in the corrected interactome network, refined by graph neural networks. An Inverted Gene Set Enrichment analysis was further applied to estimate the effect of perturbations on ATTR-related and DE genes. High probability drug candidates were discussed. Drug repositioning using systematic computational processes on an interactome network with transcriptome data were performed to screen out several potential new drug candidates for ATTR.

Effects of Flavonoid Supplementation on Athletic Performance in Healthy Adults: A Systematic Review and Meta-Analysis.

Flavonoids, known for their antioxidant properties, can prevent reactive oxygen species (ROS) and influence athletic performance through various physiological and metabolic mechanisms. However, there are conflicting results after summarizing and analyzing the relevant literature. Hence, it is warranted to evaluate the overall impact of flavonoids on athletic performance in healthy adults based on a comprehensive and systematic review and meta-analysis. After searching four databases for literature published since their respective establishments until February 2023 and conducting publication bias and quality assessments, a total of 22 studies were ultimately included. The names and doses of flavonoids, various outcome measurements, as well as types of training, were extracted from included studies. The athletic performance outcomes from the included studies were categorized into 'performance tests' and 'exercise tolerance,' depending on the type of training undertaken. Several statistical results, such as pooled effect size (ES), among others, were implemented by meta-analysis using the random effects model. The results of meta-analysis suggest that there is currently sufficient evidence (ES = -0.28; 95% confidence interval (CI): [-0.50, -0.07]; p = 0.01 and ES = 0.23; 95% CI: [0.07, 0.39]; p = 0.005) to support the notion that flavonoid supplementation enhanced athletic performance in performance tests and exercise tolerance. In addition, among the subgroups, nonsignificant results were observed for athletes (p = 0.28) and acute supplementation (p = 0.41) in performance tests, as well as athletes (p = 0.57) and acute supplementation (p = 0.44) in exercise tolerance. Meanwhile, significant results were found for non-athletes (p = 0.04) and long-term supplementation (p = 0.02) in performance tests, as well as non-athletes (p = 0.005) in performance tests and long-term supplementation (p = 0.006) in exercise tolerance. The nonsignificant results were likely due to the limitation in the number of related papers, sample sizes, optimal dosage, duration, type of flavonoids, and other factors. Therefore, future research should focus on further investigating these relationships with larger sample sizes, optimal dosage, duration, and type of flavonoids to provide more robust conclusions.

Job preference of preventive medicine students during the COVID-19 pandemic: a discrete choice experiment survey in Shandong Province, China.

BACKGROUND: Public health workers are a crucial part of the health workforce, particularly during the coronavirus disease (COVID-19) pandemic. They play an important role in achieving universal health coverage and sustainable development goals. Human resources in public health in China are in short supply, their distribution is unequal, and their turnover rate is high. A discrete choice experiment (DCE) was applied to investigate preventive medicine students' preferred job choice criteria and trends in trade-offs by calculating the marginal rate of substitution between these criteria. This study identified the properties of jobs primarily selected by preventive medicine students and estimated the monetary value of each attribute. METHODS: Based on discussions and in-depth interviews with preventive medicine students and a literature review, we developed a DCE that assessed how students' stated preferences for a certain choice were influenced by several job attributes, including location, salary, bianzhi, career development opportunities, working environment, and workload. We applied this DCE to preventive medicine students in Shandong Province, China, using a brief, structured questionnaire. Conditional logit models were used to estimate the utility of each job's attributes. Willingness to pay (WTP) was estimated as the ratio of the value of the coefficient of interest to the negative value of the cost attribute. RESULTS: A total of 307 respondents completed the questionnaire, and 261 passed the internal consistency test. All the attributes were statistically significant. Career development opportunities and work locations were the most important factors for the respondents. Preference heterogeneity existed among respondents, e.g., 3-year medical education college students placed a higher value on jobs with bianzhi compared to 5-year medical education college students. Furthermore, rural students' WTP for a job located in the county or city is much lower than that of urban students. CONCLUSIONS: The heterogeneity of attributes indicates the complexity of job preferences. Monetary and nonmonetary job characteristics significantly influenced the job preferences of preventive medicine students in China. A more effective policy intervention to attract graduates to work in rural areas should consider both job incentives and the backgrounds of preventive medicine graduates.

A prognostic model for systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

BACKGROUND: Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. RESEARCH QUESTION: To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. METHODS: A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. RESULTS: Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67-7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. CONCLUSIONS: This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Tunable bandpass microwave photonic filter with largely reconfigurable bandwidth and steep shape factor based on cascaded silicon nitride micro-ring resonators.

Bandpass microwave photonic filter (MPF) can be achieved based on the well-known phase to intensity conversion method by using phase modulation and single micro-ring resonator (MRR) notch filter. Since MRR could introduce residual phase in handling one optical sideband, the out-of-band radio frequency (RF) rejection ratio and the shape factor of the bandpass MPF are very limited. Here, by introducing another MRR to handle the other optical sideband, the residual phase can be greatly suppressed, thus the filter's performance can be greatly improved. The proposed bandpass MPF was both verified theoretically and experimentally. Compared with the single MRR, the out-of-band RF rejection ratio and the shape factor were improved by 20 dB and 1.67, respectively. Furthermore, the bandpass MPF's bandwidth is reconfigurable by adjusting the optical carrier's frequency or the two MRRs' amplitude coupling coefficients. The bandpass MPF's center frequency is also tunable by changing the resonant wavelengths of two MRRs in the opposite direction simultaneously. Experimentally, bandwidth reconfiguration from 0.38 GHz to 15.74 GHz, the shape factor optimization from 2 to 1.23, and frequency tuning from 4 GHz to 21.5 GHz were achieved. We believe that the proposed bandpass MPF has great potential for microwave photonic signal processing.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: The EXPLORER-CN Randomized Clinical Trial.

Importance: Mavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking. Objective: To evaluate the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic oHCM. Design, Setting, and Participants: This phase 3, randomized, double-blind, placebo-controlled clinical trial was conducted at 12 hospitals in China. Between January 4 and August 5, 2022, patients with oHCM and a left ventricular outflow tract (LVOT) gradient of 50 mm Hg or more and New York Heart Association (NYHA) class II or III symptoms were enrolled and received treatment for 30 weeks. Interventions: Patients were randomized 2:1 to receive mavacamten (starting at 2.5 mg once daily) or placebo for 30 weeks. Main Outcomes and Measures: The primary end point was change in Valsalva LVOT peak gradient from baseline to week 30. Left ventricular outflow tract gradients and left ventricular ejection fraction (LVEF) were assessed by echocardiography, while left ventricular mass index (LVMI) was determined by cardiac magnetic resonance imaging. Analysis was performed on an intention-to-treat basis. Results: A total of 81 patients (mean [SD] age, 51.9 [11.9] years; 58 men [71.6%]) were randomized. Mavacamten demonstrated a significant improvement in the primary end point compared with placebo (least-squares mean [LSM] difference, -70.3 mm Hg; 95% CI, -89.6 to -50.9 mm Hg; 1-sided P < .001). Similar trends were demonstrated for resting LVOT peak gradient (LSM difference, -55.0 mm Hg; 95% CI, -69.1 to -40.9 mm Hg). At week 30, more patients receiving mavacamten than placebo achieved a Valsalva LVOT peak gradient less than 30 mm Hg (48.1% [26 of 54] vs 3.7% [1 of 27]), less than 50 mm Hg (59.3% [32 of 54] vs 7.4% [2 of 27]), and NYHA class improvement (59.3% [32 of 54] vs 14.8% [4 of 27]). Greater improvements were also observed with mavacamten regarding the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (LSM difference, 10.2; 95% CI, 4.4-16.1), N-terminal pro-B-type natriuretic peptide level (proportion of geometric mean ratio, 0.18; 95% CI, 0.13-0.24), high-sensitivity cardiac troponin I level (proportion of geometric mean ratio, 0.34; 95% CI, 0.27-0.42), and LVMI (mean difference, -30.8 g/m2; 95% CI, -41.6 to -20.1 g/m2). Safety and tolerability were similar between mavacamten and placebo. No patients experienced LVEF less than 50%. Conclusions: Mavacamten significantly improved Valsalva LVOT gradient vs placebo for Chinese patients. All secondary efficacy end points were also improved. Mavacamten was well tolerated with no new safety signals. This study supports the efficacy and safety of mavacamten in diverse populations, including Chinese patients. Trial Registration: ClinicalTrials.gov Identifier: NCT05174416.

Enhanced Enzymatic Performance of ß-Mannanase Immobilized on Calcium Alginate Beads for the Generation of Mannan Oligosaccharides.

Mannan oligosaccharides (MOSs) are excellent prebiotics that are usually obtained via the enzymatic hydrolysis of mannan. In order to reduce the cost of preparing MOSs, immobilized enzymes that demonstrate good performance, require simple preparation, and are safe, inexpensive, and reusable must be developed urgently. In this study, ß-mannanase was immobilized on calcium alginate (CaAlg). Under the optimal conditions of 320 U enzyme addition, 1.6% sodium alginate, 2% CaCl2, and 1 h of immobilization time, the immobilization yield reached 68.3%. The optimum temperature and pH for the immobilized ß-mannanase (Man-CaAlg) were 75 °C and 6.0, respectively. The Man-CaAlg exhibited better thermal stability, a high degree of pH stability, and less substrate affinity than free ß-mannanase. The Man-CaAlg could be reused eight times and retained 70.34% of its activity; additionally, the Man-CaAlg showed 58.17% activity after 30 days of storage. A total of 7.94 mg/mL of MOSs, with 4.94 mg/mL of mannobiose and 3.00 mg/mL of mannotriose, were generated in the oligosaccharide production assay. It is believed that this convenient and safe strategy has great potential in the important field of the use of immobilized ß-mannanase for the production of mannan oligosaccharides.

Relationship between honesty-credit, specialty identity, career identity, and willingness to fulfill the contract among rural-oriented tuition-waived medical students of China: a cross-sectional study.

Background: The fulfillment of contractual obligations by rural-oriented tuition-waived medical students (RTMSs) to work in rural medical institutions after graduation directly impacts the improvement of rural health quality. This study aimed to not only quantitatively measure the direct impact of honesty-credit, specialty identity, and career identity on willingness to fulfill the contract of RTMSs but also to quantify the intermediary role of specialty identity and career identity between honesty-credit and willingness to fulfill the contract. The research results provided recommendations for the rural-oriented tuition-waived medical education (RTME) program to achieve its goal of training rural primary healthcare personnel. Methods: From March to May 2022, 1162 RTMSs were selected as the research objects. The honesty-credit, specialty identity, career identity, and willingness to fulfill the contract were quantitated using a self-completed questionnaire. Pearson's correlation analysis and structural equation modeling were used for statistical analysis and mediating effect evaluation. Results: A total of 455 (42.3%) RTMSs had high willingness to fulfill the contract, and honesty-credit had a significant direct positive effect on willingness (ß = 0.198, P < 0.001), specialty identity (ß = 0.653, P < 0.001), and career identity (ß = 0.180, P < 0.001). In the intermediary path between honesty-credit and willingness, career identity [95% confidence interval (CI): 0.007-0.051] had significant mediating effects. Career identity (95% CI: 0.030-0.149) also had significant mediating effects between specialty identity and willingness, and specialty identity (95% CI: 0.465-0.760) had significant mediating effects between honesty-credit and career identity. These results strongly confirmed that honesty-credit, specialty identity, and career identity are early and powerful predictors of the willingness to fulfill the contract of RTMSs. Conclusion: The honesty-credit of RTMSs can predict their willingness to fulfill the contract early, significantly and positively. For the students who fail to pass the credit assessment for many times and have a strong tendency to default, their training qualifications should be canceled in time, so that students who are truly willing to serve rural areas can enter the project, and finally achieve the policy goal of "strengthening the rural primary medical and health system".

Association Study Identified HLA-DQA1 as a Novel Genetic Risk of Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE). However, the genetic signatures of SLE-associated PAH have not been well studied. We aimed to identify genetic variants implicated in SLE-associated PAH susceptibility within the major histocompatibility complex (MHC) region and assess the contribution to clinical outcomes. METHODS: A total of 172 patients with SLE-associated PAH confirmed by right heart catheterization, 1,303 patients with SLE without PAH, and 9,906 healthy controls were included. Deep sequencing of the MHC region was performed to identify alleles, single-nucleotide polymorphisms, and amino acids. We compared patients with SLE-associated PAH with patients with SLE without PAH and healthy controls. Clinical association study was conducted to explore the contribution to phenotypes. RESULTS: A total of 19,881 genetic variants were identified within the MHC region. HLA-DQA1*03:02 was identified as a novel genetic variant associated with SLE-associated PAH in the discovery cohort (P = 5.68 × 10-12 ) and authenticated in an independent replication cohort (P = 1.30 × 10-9 ). The strongest associated amino acid position was mapped to HLA-DQα1 in the region affecting MHC/peptide-CD4+ T cell receptor affinity and antigen binding. Clinical association study demonstrated that patients with SLE-associated PAH with HLA-DQA1*03:02 had significantly lower rates of target role achievement (P = 0.005) and survival (P = 0.04). CONCLUSION: This study, based on the largest cohort of SLE-associated PAH, is the first to investigate how MHC region genetic variants contribute to SLE-associated PAH susceptibility. HLA-DQA1*03:02 is a novel genetic risk factor and a prognostic factor in SLE-associated PAH. Patients with SLE with this allele require regular monitoring and careful follow-up for early diagnosis and interventions for potential PAH.