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Abstract NASICON (Na $$_{1+x}$$ 1 + x Zr $$_2$$ 2 Si $$_x$$ x P $$_{3-x}$$ 3 - x O $$_{12}$$ 12 ) is a well-established solid-state electrolyte, renowned for its high ionic conductivity and excellent chemical stability, rendering it a promising candidate for solid-state batteries. However, the intricate influence of ion doping on their performance has been a central focus of research, with existing studies often lacking comprehensive evaluation methods. This study introduces a deep-learning-based approach to efficiently evaluate ion-doped NASICON materials. We developed a convolutional neural network (CNN) model capable of predicting the performance of various ion-doped NASICON compounds by leveraging extensive datasets from prior experimental investigation. The model demonstrated high accuracy and efficiency in predicting ionic conductivity and electrochemical properties. Key findings include the successful synthesis and validation of three NASICON materials predicted by the model, with experimental results closely matching the model’s predictions. This research not only enhances the understanding of ion-doping effects in NASICON materials but also establishes a robust framework for material design and practical applications. It bridges the gap between theoretical predictions and experimental validations. Graphical Abstract

Objective To identify risk factors associated with postoperative shoulder joint dysfunction in patients who underwent surgical intervention for acromioclavicular (AC) joint dislocation, with the aim of enhancing preoperative counselling, surgical planning, and postoperative management to optimize functional outcomes. Methods Patients who underwent surgery for AC joint dislocation between January 2018 and January 2023 at a hospital orthopaedic centre were enrolled into this retrospective study. Inclusion criteria were patients aged ≥18 years with a documented AC joint dislocation who underwent surgical treatment and had a minimum follow-up period >1 year. Patients with pre-existing shoulder conditions, prior shoulder surgeries, or incomplete medical records were excluded. Visual Analog Scale pain score ≥5 and Constant-Murley Score ≤70 was considered indicative of shoulder joint dysfunction. Statistical analyses included univariate and multivariate logistic regression to identify independent risk factors for postoperative shoulder joint dysfunction. Results Among 208 included patients, 56 (27%) exhibited shoulder joint dysfunction at the final follow-up. High-energy injury mechanisms, combined coracoclavicular ligament injuries, and lack of coronal plane congruity were identified as significant predictors of postoperative dysfunction. Specifically, high-energy injuries (odds ratio [OR] 5.493, 95% confidence interval [CI] 2.068, 14.590), combined coracoclavicular ligament injuries (OR 0.118, 95% CI 0.032, 0.432), and lack of coronal plane congruity (OR 2.540, 95% CI 1.197, 5.387) were associated with an increased risk of poor shoulder function postoperatively. Other factors, such as age, injury mechanism, and postoperative exercise compliance also contributed to the outcomes. Level of evidence: iv. Conclusions Injury mechanism, ligamentous injuries, and joint congruity are important in determining postoperative shoulder function. Accurate joint reduction and diligent postoperative rehabilitation are crucial for optimal recovery. These findings provide valuable insights for improving patient care and surgical outcomes in AC joint dislocation treatment. Further research is needed to validate these findings and explore additional factors that may influence postoperative shoulder function.

We synthesized the ferromagnetic EuAgP semiconductor and conducted a comprehensive study of its crystalline, magnetic, heat capacity, band gap, and magnetoresistance properties. Our investigation utilized a combination of X-ray diffraction, optical, and PPMS DynaCool measurements. EuAgP adopts a hexagonal structure with the P63/mmc space group. As the temperature decreases, it undergoes a magnetic phase transition from high-temperature paramagnetism to low-temperature ferromagnetism. We determined the ferromagnetic transition temperature to be TC = 16.45(1) K by fitting the measured magnetic susceptibility using a Curie-Weiss law. Heat capacity analysis of EuAgP considered contributions from electrons, phonons, and magnons, revealing η = 0.03 J/(mol·K2), indicative of semiconducting behavior. Additionally, we calculated a band gap of ∼1.324(4) eV based on absorption spectrum measurements. The resistivity versus temperature of EuAgP measured in the absence of an applied magnetic field shows a pronounced peak around TC, which diminishes rapidly with increasing applied magnetic fields, ranging from 1 to 14 T. An intriguing phenomenon emerges in the form of a distinct magnetoresistance transition, shifting from positive (e.g., 1.95% at 300 K and 14 T) to negative (e.g., −30.73% at 14.25 K and 14 T) as the temperature decreases. This behavior could be attributed to spin-disordered scattering.

Astragalus, a group of legume plants, has a pronounced rhizosphere effect. Many species of Astragalus with limited resource reserves are distributed in the high-altitude area of northern Yunnan, China. Although some of these plants have high medicinal value, the recognition of them is still at a low level. The aim of this research is to explore the species diversity of cultivable rhizofungi derived from Astragalus acaulis, A. forrestii and A. ernestii growing in a special high–cold environment of northwest Yunnan and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fermented substrate of the rhizofungus Aspergillus calidoustus AA12 derived from the plant A. acaulis showed broad-spectrum antibacterial activity and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species A. calidoustus, including sesterterpine 6-epi-ophiobolin G; three sesquiterpenes, penicisochroman A, pergillin and 7-methyl-2-(1-methylethylethlidene)-furo [3,2-H]isoquinoline-3-one; and three polyketides, trypacidin, 1,2-seco-trypacidin and questin. Among them, the compound 6-epi-ophiobolin G exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL and a prominent inhibitory effect on the biofilm of Streptococcus agalactiae at an MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half-maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizofungi from characteristic Astragalus plants in special high–cold environments and further increased the library of fungi available for natural anti-infectious product screening.

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Myasthenia gravis (MG) is a rare autoimmune disease caused by antibodies against the neuromuscular junction. PD and comorbid MG are rarely seen.Case presentationHere we report on a patient who was diagnosed with PD and MG. A 74-year-old man had a 4-year history of bradykinesia and was diagnosed with PD. He subsequently developed incomplete palpebral ptosis, apparent dropped head, and shuffling of gait. The results of neostigmine tests were positive. Repetitive nerve stimulation (RNS) showed significant decremental responses at 3 and 5 Hz in the orbicularis oculi. The patient's anti-acetylcholine receptor (anti-AchR) antibody serum level was also elevated. Meanwhile, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography–computed tomography (18F-AV133 PET-CT) scan revealed a significant decrease in uptake in the bilateral putamen. After addition of cholinesterase inhibitors, his symptoms of palpebral ptosis and head drop improved greatly and he showed a good response to levodopa.ConclusionAlthough PD with MG is rare, we still need to notice the possibility that a PD patient may have comorbid MG. The underlying mechanism of PD and comorbid MG remains unknown, but an imbalance between the neurotransmitters dopamine and acetylcholine and the immune system are likely to play significant roles in the pathogenesis. In this article, we present our case and a literature review on the co-occurrence of PD and MG, reviewing their clinical features, and discuss the underlying pathogenic mechanism of this comorbidity.

Summary: Chromium-based perovskites have gained significant interest for their magnetic and ferroelectric properties. Rare-earth orthochromates are versatile multiferroic materials in catalysts, thermistors, and non-volatile memory. We present a protocol for RECrO3 crystal growth using a laser-diode floating-zone furnace. Steps include solid-phase calcination, sintering, and shaping. We provide detailed information on crystal growth parameters and Laue diffraction analysis. The successful growth of large orthochromate single crystals paves the way for exploring their intrinsic properties and potential applications.For complete details on the use and execution of this protocol, please refer to Zhu et al.1 and Zhu et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

ObjectiveEarly identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future.MethodsDuring the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed.ResultsThe average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P

The myelin regulatory factor (MYRF; MIM# 608329) gene was first identified as a critical transcription factor involved in oligodendrocyte differentiation and central nervous system myelination. With the recent development of exome sequencing, pathogenic variants of MYRF had been considered as the cause of cardiac-urogenital syndrome (CUGS), 46,XY and 46,XX disorders/differences of sex development (DSDs), and nanophthalmos. Herein, we described a 4-year-7-month-old “girl” with ventricular septal defect, atrial septal defect, patent ductus arteriosus, severe pulmonary hypertension, moderate-to-severe tricuspid regurgitation, enlarged coronary sinus, left superior vena cava, and right lung hypoplasia at birth. Later, the patient developed short stature and amblyopia. Further examination revealed a karyotype 46,XY and visible uterus, whereas the presence of gonads were not explored. Laparoscopy revealed dysplasia of testicular gonad. Whole-exome sequencing (WES) was performed and a de novo heterozygous mutation in MYRF was identified, known as c.2817G > A/p. W939* (NM_001127392.3). Therefore, this case report presented multiple clinical manifestations with syndromic symptoms of CUGS, 46,XY DSD, and ocular symptoms. These new data expanded the phenotype of the MYRF variant and may benefit to characterize the phenotypes caused by the variants of this gene.

BackgroundVaccination remains the most effective measure to prevent SARS-CoV-2 infection and worse outcomes. However, many myasthenia gravis (MG) patients are hesitant to receive vaccine due to fear of worsening.MethodsMG patients were consecutively enrolled in two MG centers in North China. The “worsening” after vaccination was self-reported by MG patients, and severity was measured with a single simple question. The general characteristics and disease status immediately prior to the first dose were compared between the worsening and non-worsening groups. Independent factors associated with worsening were explored with multivariate regression analysis.ResultsOne hundred and seven patients were included. Eleven patients (10.3%) reported worsening after vaccination, including eight patients with mild or moderate worsening and three patients with severe worsening. Only one of them (0.9%) needed an escalation of immunosuppressive treatments. There were significant differences between the worsening and non-worsening groups in terms of Myasthenia Gravis Foundation of America classes immediately before the first dose and intervals since the last aggravation. Precipitating factors might contribute to the worsening in some patients. Logistic regression revealed that only interval since the last aggravation ≤6 months was associated with worsening after SARS-CoV-2 vaccination (P = 0.01, OR = 8.62, 95% CI: 1.93–38.46).ConclusionSARS-CoV-2 vaccines (an overwhelming majority were inactivated vaccines) were found safe in milder Chinese MG patients who finished two doses. Worsening after vaccination was more frequently seen in patients who were presumed as potentially unstable (intervals since last aggravation ≤6 months). However, mild worsening did occur in patients who were presumed to be stable. Precipitating factors should still be sought and treated for better outcome.

ABSTRACT: Many large and super-large copper deposits have been discovered and explored in the Tibet Plateau, which makes it the most important copper resource reserve and development base in China. Based on the work of the research team, the paper summarizes the geological characteristics of the main copper deposits in Tibet and puts forward a further prospecting direction. A series of large accumulated metal deposits or ore districts from subduction of Tethys oceanic crust to India-Asia collisionhave been discovered, such as Duolong Cu (Au) ore district and Jiama copper polymetallic deposit. The ore deposits in the Duolong ore district are located in the lowstand domain, the top of lowstand domain, and the highstand domain of the same magmatic-hydrothermal metallogenic system, and their relative positions are the indicators for related deposits in the Bangong Co-Nujiang metallogenic belt. The polycentric metallogenic model of the Jiama copper polymetallic deposit is an important inspiration for the exploration of the porphyry mineralization related to collision orogeny. Further mineral exploration in the Tibet Plateau should be focused on the continental volcanic rocks related to porphyry-epithermal deposits, orogenic gold deposits, hydrothermal Pb-Zn deposits related to nappe structures, skarn Cu (Au) and polymetallic deposits, and the Miocene W-Sn polymetallic deposits.©2021 China Geology Editorial Office.

Abstract Background Previous research and published literature indicate that some patients with spinal diseases who underwent percutaneous transforaminal endoscopic decompression (PTED) still suffer some discomfort in the early recovery stage in the form of pain, stiffness, and swelling. These are usually considered minor residual symptoms or normal postoperative phenomenon (NPF) in the clinic, occur frequently, and are acknowledged by surgeons worldwide. To the best of our knowledge, we report the first case of a patient who had an osteoporotic vertebral fracture (OVF) misdiagnosed as NPF after she underwent PTED as a result of lumbar disc herniation (LDH). Case presentation A 71-year-old female with Parkinson’s disease who presented with lower back pain radiating to the legs was diagnosed as LDH in L4–5, after which a PTED of L4–5 was performed, with temporary alleviation of symptoms. However, severe lower back pain recurred. Unfortunately, the recurred pain initially misdiagnosed as NPF, in fact, was finally confirmed to be OVF by CT-scan. OVF in the early stage of post-PTED seldom occurs and is rarely reported in the literature. With a percutaneous vertebroplasty, the pain was significantly relieved, and she resumed walking. After 36-weeks of follow-up, the pain improved satisfactorily. Conclusion Doctors should not immediately diagnose a relapse of back pain following PTED as NPF, and hands-on careful physical and imaging examinations are necessary to manage recurring pain rightly and timely.

Metastasis is the major cause of death in patients with pancreatic ductal adenocarcinoma (PDAC), and circulating tumor cells (CTCs) play an important role in the development of metastasis. However, few studies have uncovered the metastasis mechanism of PDAC based on CTCs. In this study, the existing bulk RNA-sequencing (bulk RNA-seq) and single-cell sequencing (scRNA-seq) data for CTCs in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database. Analysis of tumor-infiltrating immune cells (TIICs) by CIBERSORT showed that the CTCs enriched from the peripheral blood of metastatic PDAC were found to contain a high proportion of T cell regulators (Tregs) and macrophages, while the proportion of dendritic cells (DCs) was lower than that enriched from localized PDAC. Through weighted gene co-expression network analysis (WGCNA) and the result of scRNA-seq, we identified the hub module (265 genes) and 87 marker genes, respectively, which were highly associated with metastasis. The results of functional enrichment analysis indicated that the two gene sets mentioned above are mainly involved in cell adhesion and cytoskeleton and epithelial–mesenchymal transition (EMT). Finally, we found that HMGB3 was the hub gene according to the Venn diagram. The expression of HMGB3 in PDAC was significantly higher than that in normal tissues (protein and mRNA levels). HMGB3 expression was significantly positively correlated with both EMT-related molecules and CTC cluster–related markers. Furthermore, it was also found that HMGB3 mutations were favorably related to tumor-associated immune cells through the TIMER2.0 online tool. We further demonstrated that PDAC patients with higher HMGB3 expression had significantly worse overall survival (OS) in multiple datasets. In summary, our study suggests that HMGB3 is a hub gene associated with EMT in CTCs, the formation of CTC clusters, and infiltration patterns of immune cells favorable for tumor progression and metastasis to distant organs.

BackgroundThe absolute change in the severity score between the baseline and pre-specified time frame (absolute criterion) was recommended as a criterion for myasthenia gravis (MG) treatment response. But heterogeneity of disease severity might dilute major changes in individual patients. The rationality of relative criterion (improvement percentage) had not been evaluated in treatment response in patients with MG.ObjectivesTo investigate the consistency between an absolute criterion and a relative criterion in the evaluation of treatment response in patients with MG.MethodsWe retrospectively analyzed the treatment response to a 3-month standardized treatment protocol with only glucocorticoid in 257 MG patients native to immunological treatments. With the commonly used absolute criterion, cut-offs of relative criteria were generated with the receiver operating characteristic (ROC) curve in the whole cohort and in patients with different degrees of baseline severity stratified by pre-treatment quantitative myasthenia gravis score (QMGS). The consistency between absolute and relative criteria was examined with Cohen's Kappa test and Venn diagrams.ResultsThe absolute and relative criteria had an overall substantial consistency (Kappa value, 0.639, p < 0.001) in the cohort. The Kappa values were substantial to almost perfect in mild and moderate groups and moderate in severe groups between the absolute and relative criteria (all p ≤ 0.001). More patients were classified as responsive with an absolute criterion while as unresponsive with a relative criterion in the moderate and severe groups.ConclusionsThe overall consistency between absolute and relative criteria was substantial in the whole cohort. The inconsistency between the two criteria was mainly from the moderate or severe patients at the baseline.

GaFeO3-type oxides are promising multiferroic materials due to the coexistence of spontaneous magnetization and ferroelectric polarization properties at room temperature. As these ferroic properties feature a large anisotropy, single crystals are required. However, the magnetization of GaFeO3-type single crystals remains low at room temperature. In this study, we largely enhanced the magnetization at room temperature of GaFeO3-type single crystals by increasing the Fe content and co-doping Sc3+ and Al3+. Single crystals of AlxSc0.1−xGa0.6Fe1.3O3 (x = 0.01–0.04) were prepared using the optical floating-zone method. The single crystals were rod-shaped, with a diameter and length of ∼6 mm and 7 cm, respectively. X-ray diffraction measurements confirmed the ferroelectric polarization of the crystals. In addition, they exhibited room-temperature ferrimagnetism, with Curie temperature in the range of 326–338 K; the crystals exhibit magnetic anisotropy along the a-axis. The magnetization of the single crystal at 300 K and 0.3 kOe was 13 emu g−1, which is over ten times larger than those of previously reported single crystals with GaFeO3-type crystal structure.

IntroductionMinimal manifestation (MM) or better was recommended as the treatment goal for myasthenia gravis (MG). The sustainability of this status has not been described quantitatively in patients who had attained or are close to it.MethodsPatients who were with no or slight impact on daily living were recruited and followed at baseline and 3, 6, and 12 months. The included patients were classified into 3 post-intervention status (PIS) categories: remission (R), MM, and slight impact (SI). The proportion of patients belonging to real-time (not considering the intervals between assessments) and sustained (considering the intervals between assessments) PIS categories was compared at each follow-up. A sensitivity analysis (SA) cohort was established by including patients with PIS categories in all four follow-ups. The QMGS, MG-ADL, and MG-QOL15 scores in patients belonging to each PIS category at each follow-up were compared. The sustainability of the R/MM status was examined and correlated with real-time R/MM status at follow-ups.ResultsAt baseline, 376 patients could be classified, including 55 as R (14.2%), 209 as MM (54.0%), and 112 as SI (28.9%). In the whole cohort, 68.8–89.7%, 71–76.7% and 19.8–77.1% of the patients classified into real-time R, MM, and SI categories remained unchanged in each follow-up compared with the previous follow-up. The proportion of patients belonging to each real-time or sustained R/MM status at the three follow-ups was 89.7–92.1 or 60.8–67. In the SA cohort, at least 86.4% of the baseline R/MM patients remained in R/MM status till 12 months. There were no differences in keeping real-time R/MM status at 6 or 12 months between patients with and without sustained R/MM status at 3 and 6 months. There were differences in the QMGS, MG-ADL, and MG-QOL15 scores among patients belonging to each real-time category at baseline and follow-ups, ranking as R < MM < SI. The same trend was observed in patients belonging to each sustained PIS category with smaller scores than the same items of real-time categories.ConclusionThe sustainability of the R/MM status was confirmed. The R/MM status indicated a stable state of MG. The QMGS, MG-ADL, and MG-QOL15 scores may provide a quantitative reference for these PIS.

Summary: We report a combined experimental and theoretical study on intriguing magnetic properties of quasiferroelectric orthochromates. Large single crystals of the family of RECrO3 (RE = Y, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) compounds were successfully grown. Neutron Laue study indicates a good quality of the obtained single crystals. Applied magnetic field and temperature dependent magnetization measurements reveal their intrinsic magnetic properties, especially the antiferromagnetic (AFM) transition temperatures. Density functional theory studies of the electronic structures were carried out using the Perdew-Burke-Ernzerhof functional plus Hubbard U method. Crystallographic information and magnetism were theoretically optimized systematically. When RE3+ cations vary from Y3+ and Eu3+ to Lu3+ ions, the calculated t-e orbital hybridization degree and Néel temperature behave similarly to the experimentally determined AFM transition temperature with variation in cationic radius. We found that the t-e hybridization is anisotropic, causing a magnetic anisotropy of Cr3+ sublattices. This was evaluated with the nearest-neighbor J1-J2 model. Our research provides a picture of the electronic structures during the t-e hybridization process while changing RE ions and sheds light on the nature of the weak ferromagnetism coexisting with predominated antiferromagnetism. The available large RECrO3 single crystals build a platform for further studies of orthochromates.

Abstract Introduction The AP4B1 gene encodes a subunit of adaptor protein complex-4 (AP4), a component of intracellular transportation of proteins which plays important roles in neurons. Bi-allelic mutations in AP4B1 cause autosomal recessive spastic paraplegia-47(SPG47). Case presentation Here we present a Chinese patient with spastic tetraplegia, moderate psychomotor development delay and febrile seizures plus. Brain MRIs showed dilated supratentorial ventricle, thin posterior and splenium part of corpus callosum. The patient had little progress through medical treatments and rehabilitating regimens. Whole exome sequencing identified novel compound heterozygous truncating variants c.1207C > T (p.Gln403*) and c.52_53delAC (p.Cys18Glnfs*7) in AP4B1 gene. Causal mutations in AP4B1 have been reported in 29 individuals from 22 families so far, most of which are homozygous mutations. Conclusions Our study enriched the genetic and phenotypic spectrum of SPG47. Early discovery, diagnosis and proper treatment on the conditions generally increase chances of improvement on the quality of life for patients.

Common data element (CDE) is standardized data elements that describe the characteristics of diseases, with the aim of promoting the structure and standardization of data, reducing the missing of important data and narrowing the differences between different researchers in the process of data acquisition. The diversity and heterogeneity of disease phenotypes require rational preparation of CDE to reflect the disease phenotypes from multiple dimensions. This paper introduces the special problems in the establishment of CDE of myasthenia gravis (MG) and discusses the related issues on the process of developing CDE, reviews the CDE of MG domestic and abroad, and discusses the significance of CDE in the researches of MG phenotypes. DOI：10.3969/j.issn.1672⁃6731.2020.01.007

Capsaicin is a capsaicinoid in hot chili peppers, with excellent antibacterial and antimicrobial activities and a good safety profile, but its poor solubility and instability restrict its effectiveness. This limitation may be mitigated by encapsulation. Herein, capsaicin microcapsules (CCMs) were prepared through layer-by-layer self-assembly, using chitosan and carboxymethyl chitosan as shell materials. The chemical and microstructure structural characterization was evaluated by the methods of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The SEM indicated the microcapsules were irregular in shape with an average size of about 100 μm. The encapsulation had a high loading efficiency of 64.31%. FTIR and XRD revealed the absence of the interaction between the core and shell materials and the amorphous nature of the CCMs. The analysis results of the microcapsules’ release behavior showed the burst release of capsaicin in 7 days and a slow progression afterward in three solutions, with the highest release properties in a basic solution, followed by acidic and neutral salt solutions. The entomotoxicity of CCMs was conducted against Tribolium castaneum (Herbst), and its efficacy was compared with pure capsaicin. The CCMs were found to be highly effective against this pest. The LC50 value for capsaicin and its microcapsules was 31.37 and 29.75 mg/kg on adults, respectively. According to these values, T. castaneum’s development and reproduction were significantly inhibited compared with the control group. The excellent physicochemical characteristics and insecticidal performance show a high application value for integrated pest control.

BackgroundMalignant urachal tumor is a rare subtype of genitourinary cancer. Our aim was to explore the optimal chemotherapy regimens for relapsed or metastatic urachal carcinoma.Materials and MethodsWe retrospectively enrolled 24 adult patients with relapsed or metastatic urachal carcinoma from January 2014 to September 2020 at Sun Yat-sen University Cancer Center. We summarized the chemotherapy regimens and classified them as fluorouracil based, platinum based, and paclitaxel based. Nine patients received XELOX (capecitabine and oxaliplatin) regimens, seven patients received TX (paclitaxel and capecitabine) regimens, and eight of them received chemotherapy including GP (gemcitabine and cisplatin), TP (paclitaxel and cisplatin), TN (paclitaxel and nedaplatin), and tislelizumab.ResultsThe disease control rate was 75%. Among all patients, one patient treated with XELOX achieved partial remission (PR), while 17 patients showed stable disease. The median progression-free survival (PFS) and overall survival (OS) in all treated patients was 7.43 and 29.7 months, respectively. The patients receiving first-line platinum-based chemotherapy presented better PFS than those without platinum (median PFS 8.23 vs. 3.80 months, p = 0.032), but not significant for OS between two groups. There is no significant difference in PFS and OS for fluorouracil-based and paclitaxel-based groups as first-line regimen. Next-generation gene sequencing revealed TP53 mutation and low tumor mutational burden in five out of seven cases.ConclusionThe platinum-based chemotherapy regimen is effective for relapsed or metastatic urachal carcinoma.

Currently, no consensus exists regarding Sotos syndrome in the Chinese population. Here, we present a case of neonatal Sotos syndrome, followed by a retrospective analysis of five cases of neonatal Sotos syndrome, reported in China. The study subject was a twin premature infant, heavier than gestational age, with characteristic facial features, limb shaking, and hypertonia. Transient hypoglycemia, abnormal cranial magnetic resonance imaging, multiple nodules in polycystic kidneys and liver, abnormal hearing, patent ductus arteriosus, and an atrial septal defect were also noted. The subject showed overgrowth and developmental retardation at 3 months of age. Sequencing revealed a novel missense mutation, c.5000C>A, in the nuclear receptor binding the SET domain protein 1 gene, resulting in an alanine-to-glutamate substitution. The bioinformatics analysis suggested high pathogenicity at this site. This study provides insights into diagnosis of neonatal Sotos syndrome based on specific phenotypes. Subsequent treatment and follow-up should focus on developmental retardation, epilepsy, and scoliosis.

Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible “false positive report,” we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

Objectives Geographical disparities have been identified as a specific barrier to cancer screening and a cause of worse outcomes for patients with cancer. In the present study, our aim was to assess the influence of geographical disparities on the survival outcomes of patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT).Design Cohort study.Setting Guangzhou, China.Participants A total of 1002 adult patients with NPC (724 males and 278 females) who were classified by area of residence (rural or urban) received IMRT from 1 January 2010 to 31 December 2014, at Sun Yat-sen University Cancer Center. Following propensity score matching (PSM), 812 patients remained in the analysis.Main outcome measures We used PSM to reduce the bias of variables associated with treatment effects and outcome prediction. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox regression was used to identify independent prognostic factors.Results In the matched cohort, 812 patients remained in the analysis. Kaplan-Meier survival analysis revealed that the rural group was significantly associated with worse overall survival (OS, p

Bacteria growing inside biofilms are more resistant to hostile environments, conventional antibiotics, and mechanical stresses than their planktonic counterparts. It is estimated that more than 80% of microbial infections in human patients are biofilm-based, and biofouling induced by the biofilms of some bacteria causes serious ecological and economic problems throughout the world. Therefore, exploring highly effective anti-biofilm compounds has become an urgent demand for the medical and marine industries. Marine microorganisms, a well-documented and prolific source of natural products, provide an array of structurally distinct secondary metabolites with diverse biological activities. However, up to date, only a handful of anti-biofilm natural products derived from marine microorganisms have been reported. Meanwhile, it is worth noting that some promising antifouling (AF) compounds from marine microbes, particularly those that inhibit settlement of fouling invertebrate larvae and algal spores, can be considered as potential anti-biofilm agents owing to the well-known knowledge of the correlations between biofilm formation and the biofouling process of fouling organisms. In this review, a total of 112 anti-biofilm, anti-larval, and anti-algal natural products from marine microbes and 26 of their synthetic analogues are highlighted from 2000 to 2021. These compounds are introduced based on their microbial origins, and then categorized into the following different structural groups: fatty acids, butenolides, terpenoids, steroids, phenols, phenyl ethers, polyketides, alkaloids, flavonoids, amines, nucleosides, and peptides. The preliminary structure-activity relationships (SAR) of some important compounds are also briefly discussed. Finally, current challenges and future research perspectives are proposed based on opinions from many previous reviews.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (−71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration: ClinicalTrials.gov, NCT00751881;

Objective To explore the association of three single nucleotide polymorphisms (SNPs; rs228942, rs228941 and rs743777) in interleukin-2 receptor β subunit (IL-2Rβ) gene with the susceptibility and severity of myasthenia gravis (MG). Methods There were 480 MG patients and 487 normal controls enrolled in this study, and their three SNPs (rs228942, rs228941 and rs743777) in IL - 2Rβ gene were evaluated through SNPscanTM technique. Subgroups were classified by gender, age of onset, anti - acetylcholine receptor antibodies (AChR-Ab), thymus status, maximal involvement after 2 years of onset and maximal Oosterhuis score. Frequencies of alleles and genotypes were compared between MG group and control group, between MG subgroups and control group, and among subgroups under codominant, log - additive and overdominant models. Results The frequency of T allele of rs228942 in MG group was significantly higher than that in control group (χ2 = 4.692, P = 0.030, OR = 1.242, 95%CI: 1.021-1.511). There was significant difference in the frequency of rs228942 genotype between MG group and control group under log-additive model (P = 0.036, OR = 1.230, 95%CI: 1.010-1.480). The rs278942/rs228941 GT haplotype frequency in MG group was higher than that in control group (χ2 = 4.286, P = 0.038), while GG haplotype frequency in MG group was lower than that in control group ( χ2 = 5.333, P = 0.021). The frequencies of T allele of rs228942 was significantly higher in MG subgroups of onset age 15-50 years (χ2 = 7.474, P = 0.006, OR = 1.380, 95%CI: 1.095-1.740), non-thymoma (χ2 = 4.700, P = 0.030, OR = 1.261, 95%CI: 1.022-1.555) and maximal generalized involvement ( χ2 = 4.715, P = 0.030, OR = 1.287, 95% CI:1.025-1.617) than those in control group. Multivariate forward Logistic regression analysis found that onset age 15-50 years (OR = 9.026, 95%CI: 4.225-19.284; P = 0.000), onset age > 50 years (OR = 9.956, 95%CI:4.475-22.149; P = 0.000), thymoma (OR = 2.578, 95%CI: 1.393-4.773; P = 0.003) and positive AChR-Ab (OR = 1.946, 95%CI: 1.179-3.214; P = 0.009) were the independent risk factors for maximal involvement, while genotypes were not. Conclusions The rs228942 polymorphisms of IL-2Rβ gene may be associated with the susceptibility of MG, but not with the severity of MG. The rs228941 and rs743777 polymorphisms were not found to be associated with the susceptibility and severity of MG. DOI: 10.3969/j.issn.1672-6731.2016.10.006

Guillain-Barré syndrome (GBS) is an autoimmune disease mainly involving the peripheral nervous system. Since the description of its core clinical features by Guillain and Barré 100 years ago, the understanding of pathogenesis of GBS was greatly improved with recognition of its clinical diversity, and studies on its pathology, immunology, electrophysiology and animal models. This paper reviews a 100-year history of research progress in its clinical manifestation, pathophysiology and pathogenesis, diagnostic criteria, treatment and outcomes, and the relationship with vaccination in chronological order, to give a comprehensive presentation on the relationship between research progress and the development of clinical practice in GBS. DOI: 10.3969/j.issn.1672-6731.2016.09.002

We have grown La 1.37 Sr 1.63 Mn 2 O 7 single crystals with a laser-diode-heated floating-zone furnace and studied the crystallinity, structure, and magnetoresistance (MR) effect by in-house X-ray Laue diffraction, X-ray powder diffraction, and resistance measurements. The La 1.37 Sr 1.63 Mn 2 O 7 single crystal crystallizes into a tetragonal structure with space group I4/mmm at room temperature. At 0 T, the maximum resistance centers around ∼166.9 K. Below ∼35.8 K, it displays an insulating character with an increase in resistance upon cooling. An applied magnetic field of B = 7 T strongly suppresses the resistance indicative of a negative MR effect. The minimum MR value equals −91.23% at 7 T and 128.7 K. The magnetic-field-dependent resistance shows distinct features at 1.67, 140, and 322 K, from which we calculated the corresponding MR values. At 14 T and 140 K, the colossal negative MR value is down to −94.04(5)%. We schematically fit the MR values with different models for an ideal describing of the interesting features of the MR value versus B curves.

Interleukin-4 (IL-4) is a potent growth and differentiation factor for B cells which play a vital role in the pathogenesis of myasthenia gravis (MG). IL-4 exerts its function by binding to three types of IL-4 receptor (IL-4R) complexes. IL-4Rα is the key component of the IL-4R complex. We hypothesize that polymorphism of IL-4Rα gene may be associated with the susceptibility and severity of MG. A Chinese cohort of 480 MG patients and 487 healthy controls were recruited. Polymorphisms of IL-4Rα gene were determined with SNPscan™ methods and compared between MG and control groups, as well as among MG subgroups. Rs2107356 and rs1805010 were found to be associated with adult thymoma associated MG, and rs1801275 was found to be associated with adult non-thymoma AChR-Ab positive MG. We did not found association between IL-4Rα polymorphism and the severity of MG. Genetic variations of IL-4Rα were found associated with the susceptibility of MG in Chinese Han population.

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT) was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of SPP1 were found associated with the response to GC among MG patients.

OBJETIVO: Apresentar nossas experiências no tratamento de más uniões ou não consolidações talares. MÉTODO: Entre janeiro de 2000 e setembro de 2009, 26 pacientes com má união ou não-união depois de fraturas do tálus foram submetidos a tratamento cirúrgico de acordo com os diferentes tipos de deformidade talar. Os desfechos do tratamento foram avaliados pela escala tornozelo-retropé da AOFAS, assim como por radiografias simples. RESULTADOS: 20 pacientes ficaram disponíveis para acompanhamento por 30 (24 a 60) meses. Não houve problema de cicatrização ou infecção das feridas e foram obtidas uniões sólidas em todos os pacientes. As uniões radiológicas foram atingidas em tempo médio de 14 (faixa de 12 a 18) semanas. O tempo médio para concluir o apoio de carga foi 16 (faixa de 14 a 20) semanas. O escore AOFAS médio aumentou significantemente de 36,2 (27 a 43) para 85,8 (74 a 98). CONCLUSÃO: as intervenções cirúrgicas das fraturas mal-unidas ou não consolidadas dos tálus podem produzir resultados satisfatórios e o procedimento apropriado deve ser adotado, de acordo com diferentes tipos de deformidades pós-traumáticas. Nível de Evidência: IV, Estudo retrospectivo.

Symptoms of autonomic nervous system involvement and exacerbation of weakness after taking several medicines are often seen in myasthenia gravis (MG). The autonomic nervous system involvement may be a part of clinical manifestation of MG or may be caused by concomitant diseases in MG. The exacerbation of weakness may be direct effects of medicine on neuromuscular junction or complex impact resulting from various mechanisms. To elucidate the concurrence, association or causal relationship between events not only helps to explore the mechanism of diseases, but also to solve the clinical problems. DOI：10.3969/j.issn.1672⁃6731.2012.02.008

In recent decades, flipped learning has been adopted by teachers to improve learning achievement. However, it is challenging to provide all students with instant personalised guidance at the same time. To address this gap, based on Chat Generative Pre-trained Transformer (ChatGPT) and the learning scaffolding theory, I developed a ChatGPT-based flipped learning guiding approach (ChatGPT-FLGA) according to the analysis, design, development, implementation and evaluation model. To investigate the effectiveness of ChatGPT-FLGA, a quasi-experiment was conducted in the learning activities of a courseware project. One of two classes was randomly assigned to the experimental group, while the other was assigned to the control group. The students in both classes received flipped classroom instruction and conducted discussions through Tencent QQ applications, but only those in the experimental group learned with ChatGPT-FLGA. The results revealed that the ChatGPT-FLGA significantly improved students' performance, self-efficacy, learning attitudes, intrinsic motivation and creative thinking. The research findings enrich the literature on ChatGPT in flipped classrooms by addressing the influence of ChatGPT-FLGA on students' performance and perceptions.

Objective As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. Methods A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36‐Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line–C7 plumbline [CSVL–C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow‐up were compared to their preoperative results. Results Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p 0.05) but improved significantly at follow‐up (p 0.05) but considerably improved during follow‐up (p

Abstract Background Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. Methods A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. Results A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.