Updating vehicle VOCs emissions characteristics under clean air actions in a tropical city of China.

In the context of clean air actions in China, vehicle emission limits have been continuously tightened, which has facilitated the reduction of volatile organic compounds (VOCs) emissions. However, the characteristics of VOC emissions from vehicles with strict emission limits are poorly understood. This study investigated the VOC emission characteristics from vehicles under the latest standards based on tunnel measurements, and identified future control strategies for vehicle emissions. The results showed that the highest percentage of VOCs from vehicle consisted of alkanes (80.9 %), followed by aromatics (15.8 %) and alkenes (3.1 %). Alkanes had the most significant ozone formation potential due to their high concentrations, in contrast to the aromatics that have been dominant in previous studies. The measured fleet-average VOC emission factor was 71.3 mg·km-1, including tailpipe emissions of 39.6 mg·km-1 and evaporative emissions of 31.7 mg·km-1. The VOC emission factors of the subgroups were obtained. The emission of evaporated VOCs accounted for 44.5 % of the total vehicle VOC emissions, which have increased substantially from previous studies. In addition, the emission characteristics of vehicles that are under the latest emission threshold values have changed significantly, and the mixing ratio of toluene/benzene (T/B) has been updated to 3:1. This study updates the VOCs emission factors of vehicles under clean air actions and highlights the future mitigation policies should focus on reducing evaporative VOC emissions.

Myeloid­derived suppressor cell accumulation induces Treg expansion and modulates lung malignancy progression.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. The present study aimed to examine roles of T and MDSC subsets in lung malignancy. The study analyzed 102 cases with lung malignancy and 34 healthy individuals. Flow cytometry was performed for identification of T cell and MDSC subsets and their phenotypic characteristics in peripheral blood. The lung malignancy cases exhibited lower frequencies of granulocyte-like MDSCs (G-MDSCs) expressing PD-L2 and PD-L1 than healthy controls (P=0.013 and P<0.001, respectively). Additionally, there was a higher frequency of monocyte-like MDSCs (M-MDSCs) expressing PD-L1 in the peripheral blood of patients with lung malignancy than healthy controls (P<0.001). The frequencies of G-MDSCs and M-MDSCs were positively correlated with proportions of PD-1+ and CTLA-4+ regulatory T cells (Tregs). In vitro co-culture assay demonstrated M-MDSCs of lung malignancy enhanced naive T cell apoptosis and promoted Treg subset differentiation compared with M-MDSCs of healthy controls. The findings suggested accumulation of MDSC subsets in lung malignancy and MDSCs expressing PD-L2 and PD-L1 induced Treg expansion by binding to PD-1 on the surface of Tregs.

The development of local ambient air quality standards: A case study of Hainan Province, China.

The ambient air quality standard (AAQS) is a vital policy instrument for protecting the environment and human health. Hainan Province is at the forefront of China's efforts to protect its ecological environment, with an official goal to achieve world-leading air quality by 2035. However, neither the national AAQS nor the World Health Organization guideline offers sufficient guidance for improving air quality in Hainan because Hainan has well met the former while the latter is excessively stringent. Consequently, the establishment of Hainan's local AAQS becomes imperative. Nonetheless, research regarding the development of local AAQS is scarce, especially in comparatively more polluted countries such as China. The relatively high background values and significant interannual fluctuations in air pollutant concentrations in Hainan present challenges in the development of local AAQS. Our research proposes a world-class local AAQS of Hainan Province by reviewing the AAQS in major countries or regions worldwide, analyzing the influence of different statistical forms, and carefully evaluating the attainability of the standard. In the proposed AAQS, the annual mean concentration limit for PM2.5, the annual 95th percentile of daily maximum 8-h mean (MDA8) concentration limit for O3, and the peak season concentration limit for O3 are set at 10, 120, and 85 µg/m3, respectively. Our study indicates that, with effective control policies, Hainan is projected to achieve compliance with the new standard by 2035. The implementation of the local AAQS is estimated to avoid 1,526 (1,253-1,789) and 259 (132-501) premature deaths attributable to long-term exposure to PM2.5 and O3 in Hainan in 2035, respectively.

Effects of COVID-19 infection in patients with autoimmune pulmonary alveolar proteinosis: a single-center study.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease. COVID-19 is associated with worse prognosis in previous lung diseases patients. But the prognosis of aPAP patients after infection with COVID-19 is unclear. In December 2022, China experienced a large-scale outbreak of Omicron variant of the SARS-CoV-2. In this study, we aim to explore the clinical outcomes of aPAP patients infected with COVID-19. RESULTS: A total of 39 aPAP patients were included in this study. 30.77% patients had a decrease in oxygen saturation after COVID-19 infection. We compared the two groups of patients with or without decreased oxygen saturation after COVID-19 infection and found that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043), with lower baseline arterial oxygen partial pressure (74.50 ± 13.61 mmHg vs. 86.49 ± 11.92 mmHg, P = 0.009), lower baseline DLCO/VA% [77.0 (74.3, 93.6) % vs. 89.5 (78.2, 97.4) %, P = 0.036], shorter baseline 6MWD [464 (406, 538) m vs. 532 (470, 575) m, P = 0.028], higher disease severity score (P = 0.017), were more likely to have decreased oxygen saturation after COVID-19 infection. CONCLUSION: aPAP patients with poor baseline respiration have a higher probability of hypoxia after COVID-19 infection, but fatal events were rare.

[Ozone Pollution Characteristics and Formation Mechanism in a Typical Tropical Seaside City].

To investigate the pollution characteristics and formation mechanism of ambient air ozone(O3) in a typical tropical seaside city, we conducted an observational experiment on O3 and its precursors at an urban site in Haikou, Hainan Province, from June to October 2019. The O3 pollution characteristics were analyzed comprehensively; the O3-NOx-VOCs sensitivities and key precursors were determined, and the control strategies for O3 pollution were carried out. The results were as follows:1 O3 pollution in Haikou mainly occurred in September and October, with daily maximum 8-h O3 concentrations in the range of 39-190 µg·m-3, and the daily variation in O3 was unimodal, peaking at approximately 14:00. 2 The concentrations of NO2 and VOCs were higher during O3 pollution episodes than their respective mean values in Haikou City. The increased O3 precursor concentrations were an important factor leading to O3 pollution, whereas O3 pollution was also influenced by regional transport, with pollutants mainly transported from the northeastern part of Haikou City. 3 O3-NOx-VOCs sensitivity in Haikou City was in the VOCs and NOx transitional regime, and the most sensitive precursors in various months were different. O3 formation in September was sensitive to anthropogenic VOCs the most; however, in October it was sensitive to NOx. 4 In the future, the reduction ratio of VOCs to NOx should be 1:1-4:1 to control O3 pollution effectively in Haikou.

The distribution of myeloid-derived suppressor cells subsets and up-regulation of programmed death-1/PD-L1 axis in peripheral blood of adult CAP patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). METHODS: This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. RESULTS: Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. CONCLUSIONS: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.

Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients.

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.

[Spatial and Temporal Variations in Ozone Pollution and Sensitivity Characteristics in Hainan Island].

Based on ambient air quality data, meteorological observation data, and satellite remote sensing data, the temporal and spatial variations in ozone (O3) pollution, the sensitivity of O3, and its relationship with meteorological factors in Hainan Island were analyzed in this study. The results showed that the maximum daily 8-h moving mean (O3-8h) in western and northern cities in Hainan Island was higher than that in the central, eastern, and southern cities. O3-8h was the highest in 2015, and O3-8h exceeding the standard proportion was the largest in 2019. In addition, O3-8h was positively correlated with average temperature (P<0.1), sunshine duration (P<0.01), total solar radiation (P<0.01), atmospheric pressure, and average wind speed and was negatively correlated with precipitation (P<0.05) and relative humidity. The satellite remote sensing data showed that the tropospheric NO2 column concentration (NO2-OMI) and HCHO column concentration (HCHO-OMI) displayed opposite trends in Hainan Island from 2015 to 2020. Compared with those in 2015, NO2-OMI increased by 7.74% and HCHO-OMI decreased by 10.2% in 2020. Moreover, Hainan Island belongs to the NOx control area, and the FNR value exhibited a fluctuating downward trend in the past 6 years, with a trend coefficient and climatic trend rate of -0.514 and -0.123 a-1, respectively. A strong correlation was observed between meteorological factors and the FNR value of Hainan Island.

Analgesic Effect of Tuina on Rat Models with Compression of the Dorsal Root Ganglion Pain.

Neuropathic pain is a prevalent condition that affects 6.9%-10% of the population and results from nerve damage due to various etiologies, such as lumbar disc herniation, spinal canal stenosis, and intervertebral foramen stenosis. Although Tuina, a traditional Chinese manual therapy, has shown analgesic effects in clinical practice for the treatment of neuropathic pain, its underlying neurobiological mechanisms remain unclear. Animal models are essential for elucidating the basic principles of Tuina. In this study, we propose a standardized Tuina protocol for rats with compression of the dorsal root ganglion (DRG), which involves inducing DRG compression by inserting a stainless steel rod into the intervertebral foramen, performing Tuina manipulation with specific parameters of location, intensity, and frequency in a controlled environment, and assessing the behavioral and histopathological outcomes of Tuina treatment. This article also discusses the potential clinical implications and limitations of the study and suggests directions for future research on Tuina.

Tuina Manipulation to Reduce Inflammation and Cartilage Loss in Knee Osteoarthritis Rats.

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-α was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.

[Effects of Tropical Cyclones on Ozone Pollution in Hainan Island].

Based on the 181 tropical cyclones data in the western North Pacific Ocean from 2015 to 2020, hourly ozone (O3) concentration data, and meteorological observation data of 18 cities and counties in Hainan Island, this study analyzed the impacts of tropical cyclones on ozone pollution in Hainan Island. We found that 40 (22.1%) tropical cyclones experienced O3 pollution in Hainan Island during the lifetime of tropical cyclones in the past six years. During the years with more tropical cyclones, more O3- polluted days occurred in Hainan Island. Highly polluted days, which were defined as more than or equal to three cities and counties exceeding the standard, were the most serious in 2019 with 39 (54.9%) polluted days. The tropical cyclones related to high pollution (HP) showed an increasing trend, with the trend coefficient and climatic trend rate of 0.725 (exceeding the 95% significance level) and 0.667 a-1, respectively. Tropical cyclone intensity was positively correlated with the maximum 8 h moving average (O3-8h) concentration in Hainan Island. Among them, HP-type tropical cyclones accounted for 35.4% of all samples in the typhoon (TY) intensity level. Cluster analysis of tropical cyclone paths showed that tropical cyclones from the South China Sea (type A) were the most common of the 67 (37%) and were the most likely to cause large-scale and high-concentration O3 pollution events in Hainan Island. The average number of HP tropical cyclones and ρ(O3-8h) of Hainan Island in type A were 7 and 121.90 µg·m-3, respectively. In addition, the tropical cyclone centers were located generally in the middle part of the South China Sea and the western Pacific Ocean near the Bashi Strait during the HP period. The change in meteorological conditions in Hainan Island under the influence of HP tropical cyclones was conducive to the increase in O3 concentration.

[Influence of Typhoon Nangka Process on Ozone Pollution in Hainan Island].

In order to explore the influence of the 2016 typhoon Nangka on ozone (O3) concentration in Hainan Island, this study employed correlation analysis and backward trajectory simulated methods, using the hourly air quality monitoring data, meteorological data, EAR5 reanalysis data, and bright temperature (TBB) infrared from the Himawari-8 satellite from October 10 to 14, 2020. The results showed that, during the typhoon process from October 11 to 13, the O3-8h (maximum of 8 hours sliding average) concentration exceeded the standard. The averaged ρ(O3-8h) of Hainan Island reached its peak value (130.5 µg·m-3) in October 12, 2020, with the O3-8h concentration exceeding the standard in four cities and counties, in which Lingao County reached the highest concentration of 198.44 µg·m-3. During the typhoon process, the hourly O3 concentration was negatively correlated with precipitation, relative humidity, and wind speed and positively correlated with air pressure and air temperature. Moreover, the correlation coefficients between O3 with precipitation, air pressure, and relative humidity exceeded the 99.9% confidence level. The southeastern coastal provinces of China were the main contribution source area for this ozone pollution process on Hainan Island. Affected by the downdraft inside the western Pacific subtropical high (WPSH) and the downdraft outside the circumference of typhoon Nangka, vertical transport in the atmosphere appeared over the contribution source area. The meteorological conditions were favorable for atmospheric photochemical reactions. Air pollutants were transported to Hainan Island along the northeast airflow around the typhoon, resulting in the occurrence of an O3 pollution event. In addition, this study built a weather conceptual model of O3 pollution in Hainan Island affected by typhoon Nangka, which can be used as a reference for the joint pollution prevention and control by air pollution prediction, early warning, and environmental management departments.

Determinants of Progression and Mortality in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined. RESEARCH QUESTION: Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis? STUDY DESIGN AND METHODS: The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV1, and generalized linear models were used to identify variables affecting FEV1 decline. A Cox proportional hazards model was used to explore the association between clinical variables and the outcomes of death or lung transplantation in patients with lymphangioleiomyomatosis. RESULTS: VEGF-D levels and sirolimus treatment were associated with FEV1 changes and survival prognosis. Compared with patients with VEGF-D of < 800 pg/mL at baseline, patients with VEGF-D of ≥ 800 pg/mL lost FEV1 faster (SE, -38.86 mL/y; 95% CI, -73.90 to -3.82 mL/y; P = .031). The 8-year cumulative survival rates of patients with VEGF-D of ≥ 2,000 pg/mL and < 2,000 pg/mL were 82.9% and 95.1%, respectively (P = .014). The generalized linear regression model also demonstrated the benefit of delaying the decline of FEV1 by 65.56 mL/y (95% CI, 29.06-102.06 mL/y) in patients treated with sirolimus compared with those without sirolimus (P < .001). The 8-year risk of death was reduced by 85.1% (hazard ratio, 0.149; 95% CI, 0.075-0.299) after sirolimus treatment. After inverse treatment probability weighting, the risks of death in the sirolimus group were reduced by 85.6%. CT scan results of grade III severity were associated with worse progression than results of grades I or II severity. Patients with baseline FEV1 of 70% predicted or St. George's Respiratory Questionnaire Symptoms domain 50 or higher predicted a higher risk of worse survival. INTERPRETATION: Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03193892; URL: www. CLINICALTRIALS: gov.

Characterization, reactivity, source apportionment, and potential source areas of ambient volatile organic compounds in a typical tropical city.

Based on one-year observation, the concentration, sources, and potential source areas of volatile organic compounds (VOCs) were comprehensively analyzed to investigate the pollution characteristics of ambient VOCs in Haikou, China. The results showed that the annual average concentration of total VOCs (TVOCs) was 11.4 ppbV, and the composition was dominated by alkanes (8.2 ppbV, 71.4%) and alkenes (1.3 ppbV, 20.5%). The diurnal variation in the concentration of dominant VOC species showed a distinct bimodal distribution with peaks in the morning and evening. The greatest contribution to ozone formation potential (OFP) was made by alkenes (51.6%), followed by alkanes (27.2%). The concentrations of VOCs and nitrogen dioxide (NO2) in spring and summer were low, and it was difficult to generate high ozone (O3) concentrations through photochemical reactions. The significant increase in O3 concentrations in autumn and winter was mainly related to the transmission of pollutants from the northeast. Traffic sources (40.1%), industrial sources (19.4%), combustion sources (18.6%), solvent usage sources (15.5%) and plant sources (6.4%) were identified as major sources of VOCs through the positive matrix factorization (PMF) model. The southeastern coastal areas of China were identified as major potential source areas of VOCs through the potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models. Overall, the concentration of ambient VOCs in Haikou was strongly influenced by traffic sources and long-distance transport, and the control of VOCs emitted from vehicles should be strengthened to reduce the active species of ambient VOCs in Haikou, thereby reducing the generation of O3.

[Characteristics and Potential Sources of Four Ozone Pollution Processes in Hainan Province in Autumn of 2019].

Based on the air quality and meteorological monitoring data of Hainan province in autumn of 2019, this study analyzed the characteristics and potential sources for the four O3 polluted processes in Hainan province, using the methods of correlation analysis, HYSPLIT backward trajectory modeling, PSCF (potential source contribution function), and CWT (concentration weighted-trajectory). The results showed that ① the average concentrations of the maximum 8h average (O3-8h) for process 1 and process 3, which occurred from September 21st to 30th and November 3rd to 11th with the durations of 10 d and 9 d, were 145.52 µg·m-3 and 143.55 µg·m-3, respectively. Process 2 and process 4 occurred from October 18th to 21st and November 20th to 25th, with the durations of 4 d and 6 d, and the average concentrations of O3-8h were 130.79 µg·m-3 and 115.46 µg·m-3, respectively. ② High air pressure, low precipitation and relative humidity, long sunshine duration, and strong solar radiation favored the occurrence of O3-polluted weather in Hainan province. Northerly wind was conducive to the increase in O3-8h concentration, and wind speeds affected the regional distribution of high-value areas of O3-8h concentration in Hainan province. ③ Furthermore, process 1 and process 3 with more serious pollution had a larger air flow divergence, and there were two airflows originating from the inland area and the southeast coastal area, respectively. Air flow of process 2 and process 4 was relatively more concentrated with less O3 pollution and was classified as southeast coastal air flow. 4 The analysis of potential contribution sources showed that transport from Zhejiang, Jiangxi, Fujian, and Guangdong provinces were the main sources of O3 pollution in Hainan province in autumn 2019. Among them, the weight potential source contribution function (WPSCF) and weight concentration weighted-trajectory (WCWT) values were larger than 0.36 and 90 µg·m-3 in the PRD (Pearl River Delta) and western Guangdong province regions, respectively.

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

BACKGROUND: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes. METHODS: Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations. RESULTS: 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax. CONCLUSIONS: Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.

Sirolimus reduces the risk of pneumothorax recurrence in patients with lymphangioleiomyomatosis: a historical prospective self-controlled study.

BACKGROUND: Spontaneous pneumothorax has a high incidence and high rate of recurrence in patients with lymphangioleiomyomatosis (LAM). The risk factors for pneumothorax and the effects of sirolimus on pneumothorax in patients with LAM are unknown. In our study, multivariate logistic regression was applied to a cross-sectional cohort to investigate factors associated with pneumothorax in LAM patients. Kaplan-Meier analysis was applied in the historical prospective self-controlled study to determine whether sirolimus reduces the risk of pneumothorax recurrence in patients with LAM. RESULTS: Of the 399 patients registered with LAM-CHINA at our center between May 10, 2017 and August 31, 2020, 142 had a history of pneumothorax at registration. High CT grade and age at presentation ≤ 35 years were associated with a higher risk of pneumothorax in patients with LAM. Postmenopausal status was correlated with a lower risk of pneumothorax. In the historical prospective self-controlled study, the 5-year probability of pneumothorax recurrence was 80% lower in the sirolimus group than in the control group (hazard ratio for pneumothorax recurrence, 0.20; 95% CI, 0.14 to 0.30, P < 0.001 by log-rank test). CONCLUSION: Sirolimus reduced the risk of pneumothorax recurrence in LAM patients.

Lung function and air pollution exposure in adults with asthma in Beijing: a 2-year longitudinal panel study.

The effect of air pollution on the lung function of adults with asthma remains unclear to date. This study followed 112 patients with asthma at 3-month intervals for 2 years. The pollutant exposure of the participants was estimated using the inverse distance weight method. The participants were divided into three groups according to their lung function level at every visit. A linear mixed-effect model was applied to predict the change in lung function with each unit change in pollution concentration. Exposure to carbon monoxide (CO) and particles less than 2.5 micrometers in diameter (PM2.5) was negatively associated with large airway function in participants. In the severe group, exposure to chronic sulfur dioxide (SO2) was negatively associated with post-bronchodilator forced expiratory flow at 50%, between 25% and 75% of vital capacity % predicted (change of 95% CI per unit: -0.34 (-0.55, -0.12), -0.24 (-0.44, -0.03), respectively). In the mild group, the effect of SO2 on the small airways was similar to that in the severe group, and it was negatively associated with large airway function. Exposure to CO and PM2.5 was negatively associated with the large airway function of adults with asthma. The negative effects of SO2 were more evident and widely observed in adults with severe and mild asthma than in adults with moderate asthma. Patients with asthma react differently to air pollutants as evidenced by their lung function levels.

[Temporal and Spatial Variations in Ozone and Its Causes over Hainan Province from 2015 to 2020].

This study investigated temporal and spatial variations in O3-8h (defined as the maximum 8 h average result) in Hainan Province from 2015 to 2020 and further analyzed its relationships with precursors and meteorological factors based on a dataset of observations from 32 environmental monitoring stations in Hainan. Basic statistical methods, including the empirical orthogonal function (EOF), climatic tendency rate, and climatic trend coefficient analysis, were used here. The results showed that ρ(O3-8h) was higher in northern and western Hainan than that in other regions, with the maximum value occurring in Dongfang City (91.5 µg·m-3). Twelve cities and counties experienced a downward trend from 2015 to 2020, and six cities and counties reached a 95% confidence level. The variation in ρ(O3-8h) in Hainan Province demonstrated remarkable seasonal changes, which were the largest in the autumn, spring, and winter followed by the smallest in the summer, exhibiting a clear declining trend in all seasons except autumn. In addition, the cumulative variance of the first two eigenvector fields decomposed by EOF was 72.58%, which could well describe the distributed characteristics of ρ(O3-8h) in Hainan Province. The first mode reflected the consistency of ρ(O3-8h) variation, and the second mode reflected regional differences. Meanwhile, the change in ρ(O3-8h) had a good correlation with the precursors and meteorological factors. Among them, the correlation coefficients between ρ(O3-8h) and ρ(NO2), precipitation, sunshine duration, average temperature, average wind speed, atmospheric pressure, and total radiation passed the 99% confidence test. The results of multiple linear regression showed that the variation in regressed ρ(O3-8h) was consistent with the observed ρ(O3-8h), and the correlation coefficient between them was 0.853, which passed the 99.9% confidence test. The regression value explained 0.72 variance of the observed value.

Novel mutation c.1210-3C > G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.