Morphological and molecular characterization of Heterodera ripae, a new record cyst nematode in the rhizosphere soil of Fagopyrum esculentum.

Numerous plant parasitic nematodes (PPNs) have the potential to inflict considerable damage on agricultural crops. Through a comprehensive survey aimed at identifying PPNs affecting crops, cyst nematodes were isolated from the rhizosphere soil of buckwheat (Fagopyrum esculentum). Employing both molecular and morphological techniques, this cyst nematode was conclusively identified as Heterodera ripae. Notably, this represents the first documented occurrence of this particular cyst nematode species within the rhizosphere soil of F. esculentum.

Enhancing m6A modification of lncRNA through METTL3 and RBM15 to promote malignant progression in bladder cancer.

Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.

In Situ Growth of Wafer-Scale Patterned Graphene and Fabrication of Optoelectronic Artificial Synaptic Device Array Based on Graphene/n-AlGaN Heterojunction for Visual Learning.

The unique optical and electrical properties of graphene-based heterojunctions make them significant for artificial synaptic devices, promoting the advancement of biomimetic vision systems. However, mass production and integration of device arrays are necessary for visual imaging, which is still challenging due to the difficulty in direct growth of wafer-scale graphene patterns. Here, a novel strategy is proposed using photosensitive polymer as a solid carbon source for in situ growth of patterned graphene on diverse substrates. The growth mechanism during high-temperature annealing is elucidated, leading to wafer-scale graphene patterns with exceptional uniformity, ideal crystalline quality, and precise control over layer number by eliminating the release of volatile from oxygen-containing resin. The growth strategy enables the fabrication of two-inch optoelectronic artificial synaptic device array based on graphene/n-AlGaN heterojunction, which emulates key functionalities of biological synapses, including short-term plasticity, long-term plasticity, and spike-rate-dependent plasticity. Moreover, the mimicry of visual learning in the human brain is attributed to the regulation of excitatory and inhibitory post-synapse currents, following a learning rule that prioritizes initial recognition before memory formation. The duration of long-term memory reaches 10 min. The in situ growth strategy for patterned graphene represents the novelty for fabricating fundamental hardware of an artificial neuromorphic system.

Nonvolatile and reconfigurable two-terminal electro-optic duplex memristor based on III-nitride semiconductors.

With the fast development of artificial intelligence (AI), Internet of things (IOT), etc, there is an urgent need for the technology that can efficiently recognize, store and process a staggering amount of information. The AlScN material has unique advantages including immense remnant polarization, superior temperature stability and good lattice-match to other III-nitrides, making it easy to integrate with the existing advanced III-nitrides material and device technologies. However, due to the large band-gap, strong coercive field, and low photo-generated carrier generation and separation efficiency, it is difficult for AlScN itself to accumulate enough photo-generated carriers at the surface/interface to induce polarization inversion, limiting its application in in-memory sensing and computing. In this work, an electro-optic duplex memristor on a GaN/AlScN hetero-structure based Schottky diode has been realized. This two-terminal memristor shows good electrical and opto-electrical nonvolatility and reconfigurability. For both electrical and opto-electrical modes, the current on/off ratio can reach the magnitude of 104, and the resistance states can be effectively reset, written and long-termly stored. Based on this device, the "IMP" truth table and the logic "False" can be successfully reproduced, indicating the huge potential of the device in the field of in-memory sensing and computing.

Effect and Regulation Mechanism of Post-deposition Annealing on the Ferroelectric Properties of AlScN Thin Films.

Integrating ferroelectric AlScN with III-N semiconductors to enhance the performance and tunability of nitride devices requires high-quality AlScN films. This work focuses on the effect and regulation mechanism of post-annealing in pure N2 on the crystal quality and ferroelectric properties of AlScN films. It is found that the crystal quality improves with increasing annealing temperatures. Remarkably, the leakage current of AlScN films caused by grain boundaries could be reduced by four orders of magnitude after annealing at 400 °C. The crystal growth dynamics simulations and band structure calculations indicate that the energy supplied by the temperature facilitates the evolution of abnormally oriented grains to have a better c-axis orientation, resulting in the defect states at the Fermi-level disappearing, which is mainly the reason for the leakage current decrease. More interestingly, the reduction of leakage current leads to the previously leaking region exhibiting ferroelectric properties, which is of great significance to improve the ferroelectricity of AlScN and ensure the uniformity of devices. Furthermore, annealing enhances the tensile strain on the film, which flattens the energy landscape of ferroelectric switching and reduces the coercive field. However, the risk of incorporation of oxygen will also be increased if the annealing temperatures are higher than 400 °C, which will not only reduce the relative displacement of metal atoms and nitrogen atoms in AlScN but also enhance the ferroelectric depolarization field, leading to the remnant polarization decreasing dramatically. These discoveries facilitate a deeper understanding of the influencing mechanism on the ferroelectric properties of AlScN films and provide a direction for obtaining high-quality AlScN.

Visible-Light-Induced Highly Site-Selective Direct C-H Phosphorylation of Pyrrolo[2,3-d]pyrimidine Derivatives with H-Phosphine Oxides.

An efficient and highly regioselective C6-phosphorylation protocol for pyrrolo[2,3-d]pyrimidine (7-DAP) derivatives with various H-phosphine oxides induced by visible light at room temperature is described for the first time. This protocol has been successfully achieved by the combination of Na2-eosin Y as a photocatalyst and LPO as an oxidant under transition metal- and additive-free conditions. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and air tolerant conditions make this process favorable for the functional modification of pyrrolo[2,3-d]pyrimidine scaffold and enrich the phosphorylated 7-DAP compounds for further biological evaluation.

Spectral-based Quantitative Ultrasound Imaging Processing Techniques: Comparisons of RF Versus IQ Approaches.

Quantitative ultrasound (QUS) is an imaging technique which includes spectral-based parameterization. Typical spectral-based parameters include the backscatter coefficient (BSC) and attenuation coefficient slope (ACS). Traditionally, spectral-based QUS relies on the radio frequency (RF) signal to calculate the spectral-based parameters. Many clinical and research scanners only provide the in-phase and quadrature (IQ) signal. To acquire the RF data, the common approach is to convert IQ signal back into RF signal via mixing with a carrier frequency. In this study, we hypothesize that the performance, that is, accuracy and precision, of spectral-based parameters calculated directly from IQ data is as good as or better than using converted RF data. To test this hypothesis, estimation of the BSC and ACS using RF and IQ data from software, physical phantoms and in vivo rabbit data were analyzed and compared. The results indicated that there were only small differences in estimates of the BSC between when using the original RF, the IQ derived from the original RF and the RF reconverted from the IQ, that is, root mean square errors (RMSEs) were less than 0.04. Furthermore, the structural similarity index measure (SSIM) was calculated for ACS maps with a value greater than 0.96 for maps created using the original RF, IQ data and reconverted RF. On the other hand, the processing time using the IQ data compared to RF data were substantially less, that is, reduced by more than a factor of two. Therefore, this study confirms two things: (1) there is no need to convert IQ data back to RF data for conducting spectral-based QUS analysis, because the conversion from IQ back into RF data can introduce artifacts. (2) For the implementation of real-time QUS, there is an advantage to convert the original RF data into IQ data to conduct spectral-based QUS analysis because IQ data-based QUS can improve processing speed.

The AlN lattice-polarity inversion in a high-temperature-annealed c-oriented AlN/sapphire originated from the diffusion of Al and O atoms from sapphire.

AlN films are widely used owing to their superior characteristics, including an ultra-wide bandgap, high breakdown field, and radiation resistance. High-temperature annealing (HTA) makes it easy to obtain high-quality AlN films, with the advantages of a simple process, good repeatability, and low cost. However, it is always found that there is a lattice-polarity inversion from a N-polarity near the sapphire to an Al-polarity in the HTA c-oriented AlN/sapphire. Currently, the formation mechanism is still unclear, which hinders its further wide applications. Therefore, the formation mechanism of the polarity inversion and its impacts on the quality and stress profile of the upper AlN in the HTA c-oriented AlN/sapphire were investigated. The results imply that the inversion originated from the diffusion of the Al and O atoms from the sapphire. Due to the presence of abundant Al vacancies (VAl) in the upper AlN, Al atoms in the sapphire diffuse into the upper AlN during the annealing to fill the VAl, resulting in the O-terminated sapphire, leading to the N-polar AlN. Meanwhile, O atoms in the sapphire also diffuse into the upper AlN during the annealing, forming an AlxOyNz layer and causing the inversion from N- to Al-polarity. The inversion has insignificant impacts on the quality and stress distribution of the upper AlN. Besides, this study predicts the presence of a two-dimensional electron gas at the inversion interface. However, the measured electron concentration is much lower than that predicted, which may be due to the defect compensation, low polarization level, and strong impurity scattering.

Isolation, Identification, and Evaluation of the Predatory Activity of Chinese Arthrobotrys Species towards Economically Important Plant-Parasitic Nematodes.

The current investigation aimed to isolate and identify predatory fungal strains and evaluate their efficacy in mitigating the effects of plant-parasitic nematodes. We successfully isolated three distinct nematophagous fungal strains from soil samples, identified as Arthrobotrys megalosporus, A. oligospora, and A. sinensis, using conventional and molecular identification methodologies. In vitro trials illustrated the high capture efficiency of these fungi against plant-parasitic nematodes. Over an exposure period of 48 h to Aphelenchoides besseyi, Bursaphelenchus xylophilus, and Ditylenchus destructor, A. megalosporus (GUCC220044) displayed predation rates of 99.7%, 83.0%, and 21.1%, respectively. A. oligospora (GUCC220045) demonstrated predation rates of 97.3%, 97.3%, and 54.6%, and A. sinensis (GUCC220046) showed rates of 85.1%, 68.3%, and 19.0% against the same cohort of nematodes. The experimental outcomes substantiate that all three identified fungal strains demonstrate predatory activity against the tested nematodes, albeit with varying efficiencies.

Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN.

Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.

TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development.

RNA modifications, including adenine methylation (m6A) of mRNA and guanine methylation (m7G) of tRNA, are crucial for the biological function of RNA. However, the mechanism underlying the translation of specific genes synergistically mediated by dual m6A/m7G RNA modifications in bladder cancer (BCa) remains unclear. We demonstrated that m6A methyltransferase METTL3-mediated programmable m6A modification of oncogene trophoblast cell surface protein 2 (TROP2) mRNA promoted its translation during malignant transformation of bladder epithelial cells. m7G methyltransferase METTL1 enhanced TROP2 translation by mediating m7G modification of certain tRNAs. TROP2 protein inhibition decreased the proliferation and invasion of BCa cells in vitro and in vivo. Moreover, synergistical knockout of METTL3/METTL1 inhibited BCa cell proliferation, migration, and invasion; however, TROP2 overexpression partially abrogated its effect. Furthermore, TROP2 expression was significantly positively correlated with the expression levels of METTL3 and METTL1 in BCa patients. Overall, our results revealed that METTL3/METTL1-mediated dual m6A/m7G RNA modifications enhanced TROP2 translation and promoted BCa development, indicating a novel RNA epigenetic mechanism in BCa.

Remaining useful lifetime estimation for discrete power electronic devices using physics-informed neural network.

Estimation of Remaining Useful Lifetime (RUL) of discrete power electronics is important to enable predictive maintenance and ensure system safety. Conventional data-driven approaches using neural networks have been applied to address this challenge. However, due to ignoring the physical properties of the target RUL function, neural networks can result in unreasonable RUL estimates such as going upwards and wrong endings. In the paper, we apply the fundamental principle of Physics-Informed Neural Network (PINN) to enhance Recurrent Neural Network (RNN) based RUL estimation methods. Through formulating proper constraints into the loss function of neural networks, we demonstrate in our experiments with the NASA IGBT dataset that PINN can make the neural networks trained more realistically and thus achieve performance improvements in estimation error and coefficient of determination. Compared to the baseline vanilla RNN, our physics-informed RNN can improve Mean Squared Error (MSE) of out-of-sample estimation on average by 24.7% in training and by 51.3% in testing; Compared to the baseline Long Short Term Memory (LSTM, a variant of RNN), our physics-informed LSTM can improve MSE of out-of-sample estimation on average by 15.3% in training and 13.9% in testing.

Palladium-Catalyzed Highly Regioselective C6 Arylation of Pyrrolo[2,3-d]pyrimidine Derivatives with Arylboronic Acids.

A mild and selective C6 arylation strategy for pyrrolo[2,3-d]pyrimidine derivatives with arylboronic acids at room temperature is described. This unified protocol has been achieved by the synergistic combination of Pd(II)/TEMPO catalysis and CF3CO2H promotion under silver-, base-, and additive-free conditions. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and air and moisture tolerant conditions make this process attractive for the effective synthesis and modification of targeted small molecule drugs.

Bibliometric analysis of electroencephalogram research in mild cognitive impairment from 2005 to 2022.

Background: Electroencephalogram (EEG), one of the most commonly used non-invasive neurophysiological examination techniques, advanced rapidly between 2005 and 2022, particularly when it was used for the diagnosis and prognosis of mild cognitive impairment (MCI). This study used a bibliometric approach to synthesize the knowledge structure and cutting-edge hotspots of EEG application in the MCI. Methods: Related publications in the Web of Science Core Collection (WosCC) were retrieved from inception to 30 September 2022. CiteSpace, VOSviewer, and HistCite software were employed to perform bibliographic and visualization analyses. Results: Between 2005 and 2022, 2,905 studies related to the application of EEG in MCI were investigated. The United States had the highest number of publications and was at the top of the list of international collaborations. In terms of total number of articles, IRCCS San Raffaele Pisana ranked first among institutions. The Clinical Neurophysiology published the greatest number of articles. The author with the highest citations was Babiloni C. In descending order of frequency, keywords with the highest frequency were "EEG," "mild cognitive impairment," and "Alzheimer's disease". Conclusion: The application of EEG in MCI was investigated using bibliographic analysis. The research emphasis has shifted from examining local brain lesions with EEG to neural network mechanisms. The paradigm of big data and intelligent analysis is becoming more relevant in EEG analytical methods. The use of EEG to link MCI to other related neurological disorders, and to evaluate new targets for diagnosis and treatment, has become a new research trend. The above-mentioned findings have implications in the future research on the application of EEG in MCI.

Palladium-catalysed site-selective arene ortho C-H fluoroalkoxylation of 4-aryl-pyrrolo[2,3-d]pyrimidines.

A palladium-catalysed direct arene C-H fluoroalkoxylation of 4-aryl-pyrrolo[2,3-d]pyrimidine derivatives with fluorinated alcohols is described. Highly site-selective mono- or bis-fluoroalkoxylation can be achieved by tuning the reaction conditions, affording various fluoroalkoxylated pyrrolo[2,3-d]pyrimidine derivatives in moderate to good yields, which offer rational tailoring of their biological activity for their application in the field of pharmaceutical chemistry.

Collaborative hydrothermal and calcination fabrication of ZnOS heterostructures for visible-light-driven H2 production.

Photocatalytic water splitting is forecasted as a promising strategy for H2 production. In this work, novel zinc oxide/zinc sulfide (ZnOS-x) (x = 1, 2, 3 and 4) heterostructures were fabricated by a collaborative hydrothermal and calcination method with different amounts of trithiocyanuric acid. The formation of ZnOS-x heterostructures was confirmed by PXRD, XPS, and HRTEM. Moreover, ZnOS-3 nanoparticles exhibited homogeneous and smooth surface morphology structure. ZnOS-3 displayed efficient charge separation and transfer efficiency upon photoinduction. ZnOS-3 showed the highest average H2 evolution reaction rate (78.87 µmol h-1) under visible-light irradiation, which increased with increase in the ratio of trithiocyanuric acid in the ZnOS-x series. This work provides a new insight to prepare uniformly integrated heterostructures of metal oxides/sulfides for visible-light-driven H2 generation.

Research review on methods of grassland health assessment.

Grassland health refers to the degree to which the integrity of soil and ecological processes is maintained, which primarily reflects the health status and productivity of grasslands. Evaluating the degree of grassland health is vital for the sustainable develop of grasslands. There are many methods for evaluating grassland health, with advantages and disadvantages for each one. However, there is still a lack of systematic literature offering an overview of methods of grassland health assessment and their applicability. We summarized 10 methods of grassland health assessment, including vigor-organization-resilience (VOR) index evaluation model, condition-vigor-organization-resilience (CVOR) index evaluation model, principal component analysis method, analytic hierarchy process, cluster analysis method, grey relational analysis, pressure-state-response evaluation model, fuzzy comprehensive evaluation method, comprehensive evaluation model of grassland health, and evaluation model using remote sensing technology. The advantages, disadvantages, and applicability of these methods were discussed, aiming to provide scientific basis for selecting more suitable methods of grassland health assessment for different scenarios in the future.

Chiral FA Conjugated CdTe/CdS Quantum Dots for Selective Cancer Ablation.

Inducing apoptosis in cancer cells is considered a potential therapeutic mechanism underlying cancers. Here, chiral folic acid (FA) conjugated Cys-CdTe/CdS quantum dots (QDs) conjugated with a cancer-targeting ligand were fabricated to induce apoptosis in vivo. Ligand-induced chirality mechanism for FA-Cys-CdTe/CdS QDs was discussed, which is verified by density functional theory (DFT) simulation. Interestingly, we found that the circular dichroism (CD) signals of chiral QDs can effectively distinguish breast cancer cells from normal cells, where a sharp decrease in CD signal and absorption intensity can be seen. Notably, chiral FA-Cys-CdTe/CdS QDs showed significant apoptosis-inducing ability after the release of mitochondrial apoptotic factors. Furthermore, in vivo experiments showed that chiral FA-Cys-CdTe/CdS QDs provide an efficient cancer ablation through the apoptosis process with negligible toxicity, demonstrating their great potential utility in targeted anticancer agent for future clinic application.

Van der Waals Epitaxy of c-Oriented Wurtzite AlGaN on Polycrystalline Mo Substrates for Enhanced Heat Dissipation.

The epitaxy of III-nitrides on metallic substrates is competitive due to the advantages of vertical carrier injection, enhanced heat dissipation, and flexible application in various III-nitride-based devices. However, the serious lattice mismatch, atom diffusion, and interface reaction under the rigorous growth conditions have caused enormous obstacles. Based on the thermal and chemical stability of the graphene layer, we propose the van der Waals epitaxy of c-oriented wurtzite AlGaN on the polycrystalline Mo substrate by high-temperature metal-organic chemical vapor deposition. The insertion of a graphene layer interrupts the chaotic epitaxial relationship between the polycrystalline metal and epilayers, resulting in the single-crystalline orientation along the wurtzite (0002) plane and residual stress release in AlGaN because of the weak van der Waals interaction. We also demonstrate that the epitaxy of AlGaN on Mo metal possesses enhanced heat dissipation ability, in which the epilayer temperature is controlled at only 28.7 °C by the heating of a ∼54 °C hot plate. The heat dissipation enhancement for the present epitaxial structures provides a desirable strategy for the fabrication of efficient ultraviolet devices with excellent stability and lifetime.

Application of Patient-Reported Outcome Measurements in Clinical Trials in China.

Importance: Regulatory authorities, industry peers, and international health policies have emphasized the value of assessing patient-reported outcomes (PROs) in clinical studies. Despite the increase in the number of clinical studies in the last decade in China, little is known about the extent of the use of PROs. Objective: To evaluate the application and characteristics of PRO instruments as primary and secondary outcomes in randomized clinical trials in China. Design, Setting, and Participants: A cross-sectional study of interventional clinical trials conducted in China from January 1, 2010, to December 31, 2020, was performed. Data obtained from the Chinese Clinical Trial Registry and ClinicalTrials.gov databases were evaluated. Main Outcomes and Measures: Trials were categorized according to those that (1) precisely listed PRO tools as outcomes, (2) mentioned patient subjective feelings in outcomes but did not clarify which tools were used for assessment, and (3) did not mention any PRO measurements. Data on study phase, setting, participant age, and sex were extracted from trials that considered patient feelings, along with the target diseases and names of the PRO tools. Results: Among a total of 34 033 trials, 6915 (20.3%) listed the explicit PRO instruments used and 3178 (9.3%) included PRO in their outcomes but did not include the names of the assessment tools. From more than 32 million people included in the registered trials, data on 1.5 million (4.7%) patients were scientifically collected by PRO instruments, and subjective feelings were assessed for 693 867 (2.1%) participants. Pain (16.8%), cancer (15.6%), and musculoskeletal symptoms (13.3%) were the most common conditions for which PROs were precisely collected by tools. The most common tools for PRO measurements were the visual analog scale, Short-Form 36, and Hamilton Depression Scale. Conclusions and Relevance: In this cross-sectional study, the use of PROs increased during the study period in clinical trials conducted in China. However, patient opinion appears to still be rarely measured. The application of PRO is geographically unevenly distributed. Development of PRO instruments, especially those suitable for the Chinese population, may be useful. Further expansion of PROs with respect to the scope of diseases is needed to avoid missing important data.