Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Its symptoms are typically treated with levodopa or dopamine receptor agonists, but its action lacks specificity due to the wide distribution of dopamine receptors in the central nervous system and periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient retrograde adeno-associated virus (AAV), promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration. Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans.

Targeting thalamic circuits rescues motor and mood deficits in PD mice.

Although bradykinesia, tremor and rigidity are the hallmark motor defects in patients with Parkinson's disease (PD), patients also experience motor learning impairments and non-motor symptoms such as depression1. The neural circuit basis for these different symptoms of PD are not well understood. Although current treatments are effective for locomotion deficits in PD2,3, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking4-6. Here we found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN) and nucleus accumbens (NAc). Whereas PF→CPu and PF→STN circuits are critical for locomotion and motor learning, respectively, inhibition of the PF→NAc circuit induced a depression-like state. Whereas chemogenetically manipulating CPu-projecting PF neurons led to a long-term restoration of locomotion, optogenetic long-term potentiation (LTP) at PF→STN synapses restored motor learning behaviour in an acute mouse model of PD. Furthermore, activation of NAc-projecting PF neurons rescued depression-like phenotypes. Further, we identified nicotinic acetylcholine receptors capable of modulating PF circuits to rescue different PD phenotypes. Thus, targeting PF thalamic circuits may be an effective strategy for treating motor and non-motor deficits in PD.

From hidden order to antiferromagnetism: Electronic structure changes in Fe-doped URu2Si2.

In matter, any spontaneous symmetry breaking induces a phase transition characterized by an order parameter, such as the magnetization vector in ferromagnets, or a macroscopic many-electron wave function in superconductors. Phase transitions with unknown order parameter are rare but extremely appealing, as they may lead to novel physics. An emblematic and still unsolved example is the transition of the heavy fermion compound [Formula: see text] (URS) into the so-called hidden-order (HO) phase when the temperature drops below [Formula: see text] K. Here, we show that the interaction between the heavy fermion and the conduction band states near the Fermi level has a key role in the emergence of the HO phase. Using angle-resolved photoemission spectroscopy, we find that while the Fermi surfaces of the HO and of a neighboring antiferromagnetic (AFM) phase of well-defined order parameter have the same topography, they differ in the size of some, but not all, of their electron pockets. Such a nonrigid change of the electronic structure indicates that a change in the interaction strength between states near the Fermi level is a crucial ingredient for the HO to AFM phase transition.

Experimental Demonstration of a Magnetically Induced Warping Transition in a Topological Insulator Mediated by Rare-Earth Surface Dopants.

Magnetic topological insulators constitute a novel class of materials whose topological surface states (TSSs) coexist with long-range ferromagnetic order, eventually breaking time-reversal symmetry. The subsequent bandgap opening is predicted to co-occur with a distortion of the TSS warped shape from hexagonal to trigonal. We demonstrate such a transition by means of angle-resolved photoemission spectroscopy on the magnetically rare-earth (Er and Dy) surface-doped topological insulator Bi2Se2Te. Signatures of the gap opening are also observed. Moreover, increasing the dopant coverage results in a tunable p-type doping of the TSS, thereby allowing for a gradual tuning of the Fermi level toward the magnetically induced bandgap. A theoretical model where a magnetic Zeeman out-of-plane term is introduced in the Hamiltonian governing the TSS rationalizes these experimental results. Our findings offer new strategies to control magnetic interactions with TSSs and open up viable routes for the realization of the quantum anomalous Hall effect.

Flushing Toilets and Cooling Spaces with Seawater Improve Water-Energy Securities and Achieve Carbon Mitigations in Coastal Cities.

Exploring alternative water sources and improving the efficiency of energy uses are crucial approaches to strengthening the water-energy securities and achieving carbon mitigations in sub(tropical) coastal cities. Seawater use for toilet flushing and district cooling systems is reportedly practical for achieving multiaspect benefits in Hong Kong. However, the currently followed practices are yet to be systematically evaluated for scale expansions and system adaptation in other coastal cities. The significance of using seawater to enhance local water-energy securities and carbon mitigations in urban areas remains unknown. Herein, we developed a high-resolution scheme to quantify the effects of the large-scale urban use of seawater on a city's reliance on non-local and non-natural water and energy supplies and its carbon mitigation goals. We applied the developed scheme in Hong Kong, Jeddah, and Miami to assess diverse climates and urban characteristics. The annual water and energy saving potentials were found to be 16-28% and 3-11% of the annual freshwater and electricity consumption, respectively. Life cycle carbon mitigations were accomplished in the compact cities of Hong Kong and Miami (2.3 and 4.6% of the cities' mitigation goals, respectively) but not in a sprawled city like Jeddah. Moreover, our results suggest that district-level decisions could result in optimal outcomes supporting seawater use in urban areas.

[Investigation and clarification of traditional measuring units of Tibetan medicine].

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.

Utility of whole exome sequencing analysis in differentiating intrapulmonary metastatic multiple ground-glass nodules (GGNs) from multiple primary GGNs.

PURPOSE: Clinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear. EXPERIMENTAL DESIGN: Sixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs. RESULTS: A total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort. CONCLUSIONS: Our findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.

Flexoelectric Thin-Film Photodetectors.

The flexoelectric effect, which manifests itself as a strain-gradient-induced electrical polarization, has triggered great interest due to its ubiquitous existence in crystalline materials without the limitation of lattice symmetry. Here, we propose a flexoelectric photodetector based on a thin-film heterostructure. This prototypical device is demonstrated by epitaxial LaFeO3 thin films grown on LaAlO3 substrates. A giant strain gradient of the order of 106/m is achieved in LaFeO3 thin films, giving rise to an obvious flexoelectric polarization and generating a significant photovoltaic effect in the LaFeO3-based heterostructures with nanosecond response under light illumination. This work not only demonstrates a novel self-powered photodetector different from the traditional interface-type structures, such as the p-n and Schottky junctions but also opens an avenue to design practical flexoelectric devices for nanoelectronics applications.

[Clinical and microbiological characteristics of children with drowning-associated aspiration pneumonia]. / æººæ°´åŽå¸å ¥æ€§è‚ºç‚Žæ‚£å„¿çš„ä¸´åºŠç‰¹å¾åŠç— åŽŸåˆ†æž.

OBJECTIVES: To study the clinical and microbiological characteristics of children with drowning-associated aspiration pneumonia, so as to provide a reference for empirical selection of antibacterial agents. METHODS: A retrospective analysis was performed on the medical data of 185 children with drowning-associated aspiration pneumonia who were admitted to Children's Hospital of Chongqing Medical University from January 2010 to October 2020. According to the drowning environment, these children were divided into four groups: fecal group (n=44), freshwater group (n=69), swimming pool group (n=41), and contaminant water group (n=31). The clinical characteristics and pathogen detection results were reviewed and compared among the four groups. RESULTS: The 185 children had an age of 4 months to 17 years (median 34 months). Sputum cultures were performed on 157 children, and 103 were tested positive (65.6%), with 87 strains of Gram-negative bacteria (68.5%), 37 strains of Gram-positive bacteria (29.1%), and 3 strains of fungi (2.4%). Gram-negative bacteria were the main pathogen in the fecal group and the contaminant water group, accounting for 88.2% (30/34) and 78.3% (18/23), respectively. The freshwater group had a significantly higher detection rate of Gram-positive bacteria than the fecal group (P<0.008), and the swimming pool group had an equal detection rate of Gram-negative bacteria and Gram-positive bacteria. CONCLUSIONS: For pulmonary bacterial infection in children with drowning in feces or contaminant water, antibiotics against Gram-negative bacteria may be applied empirically, while for children with drowning in a swimming pool or freshwater, broad-spectrum antibiotics may be used as initial treatment, and subsequently the application of antibiotics may be adjusted according to the results of the drug sensitivity test.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

LncRNA MAFG-AS1 affects the tumorigenesis of breast cancer cells via the miR-574-5p/SOD2 axis.

Amounting evidence suggested that long non coding RNAs (lncRNAs) played vital roles in the progression of various cancers. The aim of this study is to examine the biological roles and underlying mechanisms of lncRNA MAFG-AS1 in the tumorigenesis of breast cancer (BC) cells. Here we showed that downregulation of MAFG-AS1 inhibited the viability, migration, and invasion of BC cells. Mechanism investigation showed that inhibition of MAFG-AS1 induced apoptosis via the intrinsic apoptotic pathway and overexpression of Bcl-2 could inhibited it. Further, MAFG-AS1 acts as a sponge of miR-574-5p which directly binds to SOD2 mRNA. Re-expression of SOD2 using a 3'-UTR mutant SOD2 reversed the effects of silencing of MAFG-AS1 on BC cells. Finally, downregulation of MAFG-AS1 inhibited the growth of tumour in vivo. Together, MAFG-AS1 acts as an oncogene via regulation of miR-574-5p/SOD2 axis in BC cells.

Enhancement of ferroelectricity and homogeneity of orthorhombic phase in Hf0.5Zr0.5O2thin films.

By adoption of a high permittivity ZrO2capping layer (ZOCL), enhanced ferroelectric properties were achieved in the Hf0.5Zr0.5O2(HZO) thin films. For HZO thin film with 10 Å ZOCL, the 2Prvalue can reach as high as ∼43.1µC cm-2under a sweep electric field of 3 MV cm-1. In addition, a reduced coercive field of 1.5 MV cm-1was observed, which is comparable to that of HZO with metallic CL. Furthermore, the homogeneity of ferroelectric orthorhombic phase in HZO films was observed to be clearly increased, as evidenced by nanoscale piezoelectric force microscopy measurements. These results demonstrate that ZOCL is very favorable for high performance ferroelectric HZO films and their future device applications.

Moesin as a prognostic indicator of lung adenocarcinoma improves prognosis by enhancing immune lymphocyte infiltration.

BACKGROUND: Ezrin-radixin-moesin (ERM) have been explored in many cancer processes. Moesin, as its component, has also been found to play an important role in the prognosis of cancer patients, tumor metastasis, drug resistance, and others. Especially in regulating the immunity, but most results came from direct studies on immune cells, there is no clear conclusion on whether moesin has similar effects in tumor cells. And moesin has certain research results in many cancers in other aspects, but there are few about moesin in lung adenocarcinoma (LUAD). METHODS: We detect the expression of moesin in 82 LUAD and matched normal tissue samples by immunohistochemistry. Besides, for the pathological feature, we did a detailed statistical analysis. And with the help of various databases, we have done in-depth exploration of moesin's ability to enhance the extent of immune lymphocyte infiltration. RESULTS: Moesin is a poor expression in lung cancer tissues than the corresponding normal samples. And this phenomenon had a strongly associated with the prognosis and TNM stage of these LUAD patients. Moesin can enhance the infiltration of multiple immune lymphocytes in lung cancer. And this may be related to the interaction between moesin and various inflammatory molecules. CONCLUSIONS: Moesin is a newly index for the prognosis of LUAD and improves the prognosis of LUAD patients by regulating a variety of inflammation-related molecules to enhance immune lymphocytes infiltration.

REPORT- Clinical outcomes of using second - versus first-Generation EGFR-tkis for the First-Line treatment of advanced NSCLC patients with EGFR mutations: A meta-analysis.

First-generation EGFR-TKIs (gefitinib/erlotinib) and second-generation EGFR-TKI (afatinib) have become the current first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC), however, the effects of using second-generation EGFR-TKIs compared to those of using first-generation EGFR-TKIs as a first-line treatment for NSCLC patients with EGFR mutations remain unknown. We conducted this meta-analysis based on 4 retrospective and 2 randomized controlled studies published between 2016 and 2018. We surveyed the effectiveness of afatinib/dacomitinib and gefitinib/erlotinib as first-line treatments for stage III-IV EGFR-mutated NSCLC patients. The combined hazard ratio (HR) for the progression free survival (PFS) of second-generation EGFR-TKI group versus that first-generation drug group was 0.64 [95% confidence interval (95% CI) 0.55-0.74; P<0.001], demonstrating a superior PFS in the second-generation group. This outcome coincided with the subgroup analyses comparing the PFS of patients with EGFR exon 19 deletion (HR = 0.68 [95% CI 0.55-0.83; P = 0.0002]) or L858R mutation (HR = 0.64 [95% CI 0.51-0.81; p=0.0002]). Meanwhile, second-generation drugs could to significantly improve the time to progression (TTFs) compared to first-generation drugs (HR = 0.81 [95% CI 0.67-0.89; P = 0.03]). Afatinib and dacomitinib may be the superior first-line treatment for advanced NSCLC patients with EGFR mutations.

Consistency between nasopharyngeal aspirates and bronchoalveolar lavage fluid in pathogen detection in children with pneumonia: an analysis of 533 cases. / 533ä¾‹è‚ºç‚Žå„¿ç«¥é¼»å’½æŠ½å¸ç‰©å’Œæ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—æ¶²çš„ç— åŽŸæ£€å‡ºä¸€è‡´æ€§åˆ†æž.

OBJECTIVES: To study the consistency between nasopharyngeal aspirates (NPA) and bronchoalveolar lavage fluid (BALF) in pathogen detection in children with pneumonia. METHODS: A retrospective analysis was performed on the data of pathogens detected in 533 children with pneumonia from February 2017 to March 2020. The paired McNemar's test was used to compare the difference in pathogen detection between NPA and BALF groups. The Kappa coefficient was used to analyze the consistency in pathogen detection between the two groups. RESULTS: NPA had a sensitivity of 28%, a specificity of 74%, a positive predictive value of 14%, and a negative predictive value of 91% in detecting bacteria, and a Kappa coefficient of 0.013 suggested poor consistency between NPA and BALF. NPA had a sensitivity of 52%, a specificity of 81%, a positive predictive value of 24%, and a negative predictive value of 94% in detecting viruses, and a Kappa coefficient of 0.213 suggested poor consistency between NPA and BALF. NPA had a sensitivity of 78%, a specificity of 71%, a positive predictive value of 49%, and a negative predictive value of 90% in detecting Mycoplasma pneumoniae, and a Kappa coefficient of 0.407 suggested moderate consistency between NPA and BALF. CONCLUSIONS: There is poor consistency between NPA and BALF in the detection of bacteria and viruses, and clinicians should be cautious in diagnosing lower respiratory tract infection based on bacteria or viruses detected in NPA. There is moderate consistency between NPA and BALF in the detection of Mycoplasma pneumoniae, suggesting that it may be reliable to diagnose lower respiratory tract infection based on Mycoplasma pneumoniae detected in NPA, while comprehensive judgment in combination with clinical conditions is needed.

Thickness-dependent magnetotransport properties in 1T VSe2 single crystals prepared by chemical vapor deposition.

Two-dimensional (2D) metallic transition metal dichalcogenides (TMDs) exhibit fascinating quantum effects, such as charge-density-wave (CDW) and weak antilocalization (WAL) effect. Herein, low temperature synthesis of 1T phase VSe2 single crystals with thickness ranging from 3 to 41 nm by chemical vapor deposition (CVD) is reported. The VSe2 shows a decreasing phase transition temperature of the CDW when the thickness is decreased. Moreover, low-temperature magnetotransport measurements demonstrate a linear positive and non-saturating magnetoresistance (MR) of 35% from a 35 nm thick VSe2 at 15 T and 2 K due to CDW induce mobility fluctuations. Surprisingly, Kohler's rule analysis of the MR reveals the non-applicability of Kohler's rule for temperature above 50 K indicating that the MR behavior cannot be described in terms of semiclassical transport on a single Fermi surface with a single scattering time. Furthermore, WAL effect is observed in the 4.2 nm thick VSe2 at low magnetic fields at 2 K, revealing the contribution of the quantum interference effect at the 2D limit. The phase coherence length [Formula: see text] and spin-orbit scattering length [Formula: see text] were determined to be 73 nm and 18 nm at 2 K, respectively. Our work opens new avenues to study the fundamental quantum phenomena in CVD-deposited TMDs.

Probing the reaction mechanism of Al/CuO nanocomposites doped with ammonium perchlorate.

The oxide shell of Al nanoparticles (Al NPs) prevents further reaction of Al/CuO nanothermites which reduces Al utilization efficiency and the performance of the nanothermites. However, the performance of Al/CuO nanothermites can be improved by adding ammonium perchlorate (AP). In this work, in order to confirm and explain the enhancement mechanism of AP on Al/CuO nanothermites, Al/CuO/NC and Al/CuO/NC/AP composites were prepared using the electrospray method. The composites were characterized by differential scanning calorimetry/thermogravimetric, x-ray diffraction, scanning electron microscope and transmission electron microscopy. Meanwhile, the ignition temperature and the time-resolved analysis of the rapid pyrolysis chemistry of the composites were tested using T-jump and time-of-flight mass spectrometry, respectively. The results show that Al NPs of Al/CuO/NC/AP composite are hollow compared to Al/CuO/NC composite after reaction. Al NPs and CuO NPs reduce the decomposition temperature and facilitate the rapid decomposition of the AP, and the decomposition products of the AP can destroy the oxidation layer of Al NPs. This result facilitates the further conduct of the thermite reaction. A mutually reinforcing relationship exists between the Al/CuO/NC composites and AP.

From nanoparticles to on-chip 3D nanothermite: electrospray deposition of reactive Al/CuO@NC onto semiconductor bridge and its application for rapid ignition.

Nanothermites composed of nano-fuels and oxidants are attractive energetic materials, which have potential applications in microscale energy-demanding systems. Herein, nano-Al/CuO with nitrocellulose (NC) binder have been bottom-up assembled on semiconductor bridge (SCB) chip by electrospray, from nanoparticles to three-dimensional (3D) deposited structure. The morphological and compositional characterization confirms the constituents in Al/CuO@NC are homogeneously mixed at nano scale and the 3D structure at micro scale is tunable. The as-deposited Al/CuO@NC exhibits excellent energy output and superior chemical reactivity. Specifically, the heat release of Al/CuO@NC (1179.5 J g-1) is higher than that of random mixed Al/CuO (730.9 J g-1). Benefiting from outstanding exothermic properties, the material integrated with SCB initiator chip (Al/CuO@NC-SCB) for potential ignition application was investigated. The Al/CuO@NC-SCB micro energetic initiator can be functioned rapidly (with delay time of 2.8 µs) and exhibits superb ignition performances with violent explosion process, high combustion temperature (4636 °C) and successful ignition of B/KNO3 propellant, in comparison to SCB initiator. The strategy provides promising route to introduce nano reactive particles into various functional energy-demanding systems for potential energetic applications.

Test of transformation mechanism of food waste and its impacts on sulfide and methane production in the sewer system.

Food waste (FW) management has become an important issue worldwide. Diverting FW into the sewer system is considered promising to tackle the FW issue. However, the transformation of FW in sewers and its impact on the sewer process have not received adequate attention due to the overlooked sewer networks. In this study, a laboratory-scale sewer reactor system was established to investigate the transformation of FW and the production of sulfide and methane under anaerobic conditions. The transformation of FW in the sewer reactor could result in an increase in the substrate level through hydrolyzing and converting biodegradable substances into preferred substrates. Moreover, the generated substrates from the addition of FW were preferable for the metabolism of key microbes in sewer biofilms. As a result, methane production from the sewer reactor could be enhanced from the addition of FW, whereas sulfide production was not affected at a low sulfate concentration. The findings of this study suggest that the diversion of FW may exert an adverse impact on sewers and the environment in terms of greenhouse gas emission. Hence, more research is necessary to clarify the detailed impacts on FW management and wastewater treatment.

[Influencing factors for the clinical effect of bronchoalveolar lavage in children with Mycoplasma pneumoniae pneumonia and atelectasis].

OBJECTIVE: To study the influencing factors for the clinical effect of bronchoalveolar lavage (BAL) in children with Mycoplasma pneumoniae pneumonia (MPP) and atelectasis. METHODS: A total of 75 children with MPP and atelectasis were divided into a good response group with 51 children and a poor response group with 24 children according to the clinical effect of BAL treatment. LASSO logistic regression analysis was used to investigate the factors influencing the clinical effect of BAL treatment. The receiver operating characteristic (ROC) curve and restricted cubic spline model analysis were used to evaluate the value of the course of the disease at the time of BAL treatment in predicting the clinical effect of BAL treatment. RESULTS: Compared with the good response group, the poor response group had a significantly lower percentage of lymphocytes in bronchoalveolar lavage fluid, a significantly higher proportion of children with atelectasis of two or more lung lobes or stenosis of the bronchial cavity or opening caused by inflammation, and a significantly longer course of the disease at the time of BAL treatment and azithromycin treatment (P<0.05). The LASSO logistic regression analysis showed that a prolonged course of the disease at the time of BAL treatment (OR=1.23), atelectasis of two or more lung lobes (OR=11.99), and stenosis of the bronchial cavity or opening caused by inflammation (OR=5.31) were independent risk factors for poor clinical effect of BAL treatment (P<0.05). The ROC curve analysis showed that the course of disease of ≥11.5 days at the time of BAL treatment suggested a poor clinical effect of BAL treatment, with a sensitivity of 91.7% and a specificity of 54.9%. The restricted cubic spline model analysis showed that there was a non-linear dose-response relationship between the course of disease at the time of BAL treatment and the clinical effect of BAL treatment (P<0.05). CONCLUSIONS: Early BAL treatment may have a good clinical effect in children with MPP and atelectasis. Atelectasis of two or more lung lobes and inflammation-induced stenosis of the bronchial cavity or opening shown under bronchoscope may indicate a poor clinical effect of BAL treatment.