Clinical characteristics and logistic regression analysis of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

PURPOSE: To investigate macrolide-resistant Mycobacterium pneumoniae (MRMP) pneumonia in children and construct a logistic regression model for mutations in the Mycoplasma pneumoniae drug-resistant gene. METHODS: Clinical data of 281 children were analyzed. Sequencing confirmed a mutation at the A2063G locus of the 23 S rRNA gene in 227 children (A2063G group); 54 children showed no mutations (non-MRMP [NMRMP] group). We compared clinical features, laboratory tests, imaging, and bronchoscopy results and constructed a multifactorial logistic regression model to analyze risk and protective factors. RESULTS: The A2063G group had longer durations of fever and hospitalization before admission, a higher proportion of treatment with sodium methylprednisolone succinate (MPS)/dexamethasone, longer time to discontinue hormones, and higher probability of combined infections. Monocyte percentage was significantly higher in the A2063G group. Imaging suggested a higher incidence of infections in the right lung compared to both lungs. Univariate analysis revealed fever duration before admission, hormone dose and duration, monocyte percentage, and mixed infections as risk factors for Mycoplasma pneumoniae infection with the A2063G mutation. The logistic regression model showed that mixed infections were an independent risk factor for the A2063G locus mutation, whereas hormone dose was a protective factor. CONCLUSION: A prevalence of macrolide resistance of 80.8% among children was observed in the region. Logistic regression analysis revealed that co-infection with other respiratory pathogens is an independent risk factor for the development of resistance genes, while the use of hormone dosage acts as a protective factor.

Cooperative Sentinel Surveillance of Malaria in Laiza and Nearby Areas of Myanmar and Importation Threat Monitoring - China, 2019-2023.

Introduction: Laiza and nearby areas (LNA) in Myanmar are identified as the primary malaria hotspots in the bordering regions of Yunnan Province, China. Methods: Six sentinel surveillance sites were established at the China-Myanmar border in LNA to monitor malaria. Data from 2019 was used as a baseline to analyze malaria incidence and trends in LNA and Myanmar, as well as the importation of malaria cases into China from 2019 to 2023. Results: Plasmodium vivax was the predominant species, representing 99.95% (14,060/14,066) of confirmed malaria cases in LNA. A total of 8,356 malaria cases were identified in 2023, with an annual parasite incidence (API) of 19.78 per 100 person-years. Compared to 2019, the incidence rate ratio was 21.47 (95% confidence interval: 18.84, 24.48), indicating that the API in 2023 was 21.47 times higher than that in 2019. In Yunnan, out of 1,016 reported cases, 545 imported cases (53.64%) originated from LNA and spread to 18 (13.95%) out of 129 counties. Ten provinces in China, including Yunnan, reported imported malaria cases from LNA in Myanmar. Conclusions: The increase in population, particularly among internally displaced persons, along with inadequate healthcare services, has led to a notable resurgence of malaria in LNA. This resurgence poses a risk to preventing the re-emergence of malaria transmission in China. There is an urgent need for novel collaborative policies, as well as financial and technical assistance, to enhance malaria control efforts in LNA, Myanmar.

Isodonxiaoluzhiensis (Lamiaceae, Nepetoideae), a new species from Yunnan, southwest China.

Isodonxiaoluzhiensis, a new species of the tribe Ocimeae in family Lamiaceae, is described and illustrated. The new species is known only from the type locality, Xiaoluzhi village in Luzhijang dry-hot valley of Yimen County, central Yunnan, southwest China. It is characterized by having a procumbent habit, gracile stems and branches, relatively small leaves and flowers, and the phenology of flowering in winter. The morphological comparisons with its putative closest relatives (I.adenanthus and I.hsiwenii) are also presented.

Exploring the potential molecular mechanism of Gualou Guizhi decoction in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking.

BACKGROUND: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Gualou Guizhi Decoction (GGD) has long been used as a folk medicine for the treatment of rheumatic diseases, but its bioactive components and therapeutic mechanisms are still unclear. METHODS: An integrated approach using network pharmacology and molecular docking and using methotrexate as a positive control drug. RESULTS: We obtained 157 active ingredients of GGD, 7542 RA disease targets and 49 intersecting targets. GO and KEGG enrichment analysis revealed that their functions were mainly related to cytokine active metal ion binding, enzyme binding and DNA binding, and enriched in TNF signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, RA pathway and other signaling pathways that are closely related to RA. The molecular docking results show that the effector components of GGD bind better to the core targets of RA, and some are even better than methotrexate. CONCLUSION: The therapeutic effect of GGD for RA is achieved by affecting the core targets such as VEGFA, IL-1ß, IL6, CXCL8, CCL2, and JUN, which together interfere with the tumor necrosis factor signaling pathway and RA pathway to treat RA. The above study provides new ideas for further exploration of this classic formula in the future.

[Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification].

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1ß(IL-1ß). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1ß, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Exploring the chondroprotective effect of Chaenomeles speciosa on Glucose-6-Phosphate Isomerase model mice using an integrated approach of network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Chaenomeles speciosa (CSP) (Chinese Pinyin: mugua) is a medicinal and food herb that has long been used as a folk medicine for rheumatic diseases, yet its bioactive components and therapeutic mechanisms are not clear. AIM OF THE STUDY: Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action. MATERIALS AND METHODS: In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA. RESULTS: Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1ß, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1ß, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction. CONCLUSION: This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA.

Serological surveillance on potential Plasmodium vivax exposure risk in a post-elimination setting.

China was declared malaria free in June of 2021. In the post-elimination setting, vigilant surveillance is essential to sustain malaria free status. Serological surveillance has been recognized as an efficient tool for assessing the immunity levels and exposure risk in a population. In this study, a cross-sectional serological survey was conducted in Yingjiang County, China, in August-September, 2021. The study sites were villages along the borders with Myanmar, which have no local transmission since the last indigenous case registered in 2016. A total of 923 participants from six villages were enrolled. The majority was aged > 36 years (56.12%) and 12.46% (115/923) participants had experienced malaria infection at least once. A magnetic- bead-based assay was used to test antibodies against Plasmodium vivax antigen PvMSP-119 to evaluate the prevalence of antibody positive subjects. A reversible catalytic model was used to assess the risk of exposure. The prevalence of anti-PvMSP-119 IgG was 12.84% [95% confidence interval (CI): 9.22%-16.47%], 13.93% (95% CI: 10.11%-17.74%), and 3.57% (95% CI: 1.40%-5.75%) in three different line-of-defense areas, which differed significantly (P < 0.0001). The prevalence of anti-PvMSP-119 IgG increased with age and no statistically significant difference was detected between the sexes. The reversible catalytic model indicated that the seropositive conversion rate and seronegative reversion rate were 0.0042, 0.0034, 0.0032 and 0.0024, 0.0004, 0.0065 in the first-, second-line-of-defense area and total areas, respectively, and the fitted value did not differ significantly from the observed value (P > 0.1). Although this study found the prevalence of antibody-positive subjects and the seroconversion rate in this post-elimination setting were lower than that in transmission setting, the population still had an exposure risk. Serological surveillance should be considered in post-elimination settings to provide valuable information with which to evaluate the risk of malaria re-establishment.

Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region.

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.

Genetic diversity of transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 in Plasmodium vivax isolates from China.

BACKGROUND: Transmission-blocking vaccines (TBVs) target the sexual stages of malaria parasites to reduce or interrupt the transmission cycle in human and mosquito populations. The genetic diversity of TBVs candidate antigens, Pvs25 and Pvs28, in Plasmodium vivax could provide evidence for the development of TBVs. METHODS: Dry blood spots from P. vivax patients were collected from Dandong, Suining, Hainan, Nyingchi, Tengchong, and Yingjiang in China. The pvs25 and pvs28 genes were amplified and sequenced. The genetic diversity of pvs25 and pvs28 were analyzed using DNASTAR, MEGA6, and DnaSP 5.0 programs. RESULTS: A total of 377 samples were collected, among which 324 and 272 samples were successfully amplified in the pvs25 and pvs28 genes, respectively. Eight haplotypes were identified in Pvs25, for which the predominant mutation was I130T with 100% prevalence. A variety of 22 haplotypes in Pvs28 were identified. The number of GSGGE/D repeats of Pvs28 was a range of 4-8, among which, high (7-8) and low (4-5) copy numbers of tandem repeats were found in haplotypes H2 and H17, respectively. The nucleotide diversity of pvs28 (π = 0.00305 ± 0.00061) was slightly higher than that of pvs25 (π = 0.00146 ± 0.00007), thus they were not significantly different (P > 0.05). The Tajima's D value of pvs25 was positive whereas pvs28 was negative, which indicated that both genes were affected by natural selection. CONCLUSION: The genetic diversity of pvs25 and pvs28 genes in China was relatively limited, which provided valuable information for TBVs design and optimization.

Expression and Clinical Trends of Pct Combined with Lactate Clearance in Sepsis.

Objective: To study the expression and clinical trend of procalcitonin (Pct) + lactate clearance in sepsis. Methods: A total of 63 septic shock patients enrolled in our hospital from March 2018 to March 2021 were recruited as group A, and the 87 septic patients admitted during the same period were recruited as group B. The Pct, lactic acid, and lactate clearance were compared between the two groups. Results: The Pct and lactic acid in group A were higher than those in group B at the time of diagnosis, 1 d, 2 d, and 3 d after treatment, but the lactate clearance rate at 1 d, 2 d, and 3 d after treatment was lower than that in group B (P < 0.05). The Pct and lactate at the time of diagnosis, 1 d, 2 d, and 3 d after treatment in the good prognosis group were lower than those in the poor prognosis group, but the lactate clearance rate at 1 d, 2 d, and 3 d after treatment was higher than that in the poor prognosis group (P < 0.05). Disease severity and prognosis were positively correlated with Pct and lactate, but negatively correlated with lactate clearance rate (P < 0.05). Conclusions: Pct and lactate clearance rate might serve as accurate predictors of the severity of sepsis and prognosis. It merits promotion in clinical setting.

Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar.

BACKGROUND: Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region. METHODS: Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance. RESULTS: A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 "AAG" insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%). CONCLUSIONS: This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region.

In Vitro Toxicological Investigation and Risk Assessment of E-Cigarette Aerosols Based on a Novel Solvent-Free Extraction Method.

Cigarettes, potentially safer alternatives to combustible cigarettes, have been reported to increase the health risk for long-term users, so accumulating information about their potential toxicity is of great concern. However, toxicological evaluations of e-cigarette aerosols are limited, which may be attributed to the lack of a simple and efficient extraction method. Here, we developed a high-speed centrifugal method for extracting e-cigarette aerosol collected mass (ACM) and prepared ACM samples of 26 representative e-cigarettes, and 10 samples were further selected based on their cytotoxicity for systematic toxicological assessments. The average extraction efficiency of ACM, primary aerosol components, and typical carbonyls exceeded 85%. The toxicological evaluation showed that the IC50 value range of e-cigarettes for cytotoxicity was 2-52 mg/mL ACM, all e-cigarettes can induce the risk of DNA damage, mitochondrial depolarization, and c-Jun-related signal disturbances; most e-cigarettes significantly caused disturbance of oxidative stress balance. E-cigarettes with higher cytotoxicity appeared to cause a higher degree of damage, while no e-cigarette promoted mutagenicity and cytochrome c release. The toxicity difference among e-cigarettes using nicotine equivalent was significantly lower than that of ACM. This study provides a novel extraction method and a comprehensive in vitro toxicity risk profile of e-cigarette aerosols.

Indigoferavallicola (Fabaceae), a new species from Yunnan, southwest China.

Indigoferavallicola (Fabaceae), a new species is described and illustrated. This plant is only found from two localities in the central Yunnan Province, southwest China. It is characterized by having the prostrate habit, usually 13-17-foliolate leaves and the relatively small (3-5 mm long) flowers. Morphological comparisons with its closest relatives, I.rigioclada, I.franchetii, I.chaetodonta, and I.henryi are also presented.

Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

Novel Solvent-Free Extraction Method for Analyzing Tobacco Heating Product Aerosols: An Analytical and In Vitro Toxicological Five-Way Product Comparison.

Harmful and potentially harmful constituents (HPHCs) in tobacco smoke are thought to be responsible for the increased health risks. Tobacco heating products (THPs) heat tobacco instead of burning it to achieve significantly fewer toxicants than conventional cigarettes. To assess the toxicity of THP aerosols, it is often desirable to extract the main constituents using a solvent method. In this study, we developed a high-speed centrifugal method for extracting the total particulate matter (TPM) from THPs to quantitatively compare the toxicity of different THPs and conventional cigarettes. Its TPM extraction efficiency exceeded 85%, and the primary aerosol components and typical HPHCs were comparable to those of the solvent method. The TPMs extracted from five THPs were subjected to 14 in vitro toxicology assessments, and the results were compared with those of a 3R4F reference cigarette. Physical separation can improve biases from solvent selectivity and potential interactions between solvent and aerosol constituents. By eliminating solvent influence, the extraction method could achieve high-dose exposures, enabling the toxicity comparison of different THPs. The relative toxicity of the THPs differed under different dosage units, including the TPM concentration, nicotine equivalent, and puff number.

A retrospective analysis of malaria epidemiological characteristics in Yingjiang County on the China-Myanmar border.

Yingjiang County, which is on the China-Myanmar border, is the main focus for malaria elimination in China. The epidemiological characteristics of malaria in Yingjiang County were analysed in a retrospective analysis. A total of 895 malaria cases were reported in Yingjiang County between 2013 and 2019. The majority of cases occurred in males (70.7%) and individuals aged 19-59 years (77.3%). Plasmodium vivax was the predominant species (96.6%). The number of indigenous cases decreased gradually and since 2017, no indigenous cases have been reported. Malaria cases were mainly distributed in the southern and southwestern areas of the county; 55.6% of the indigenous cases were reported in Nabang Township, which also had the highest risk of imported malaria. The "1-3-7" approach has been implemented effectively, with 100% of cases reported within 24 h, 88.9% cases investigated and confirmed within 3 days and 98.5% of foci responded to within 7 days. Although malaria elimination has been achieved in Yingjiang County, sustaining elimination and preventing the re-establishment of malaria require the continued strengthening of case detection, surveillance and response systems targeting the migrant population in border areas.

Application of bedside ultrasound in predicting the outcome of weaning from mechanical ventilation in elderly patients.

BACKGROUND: With the increased ageing of society, more and more elderly people are admitted to the intensive care unit, How to accurately predict whether elderly patients can successfully wean from the ventilator is more complicated. Diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were measured by bedside ultrasound to assess diaphragm function. The lung ultrasound score (LUS) and the rapid shallow breathing index (RBSI) were used as indices of diaphragm function to predict the outcome of weaning from mechanical ventilation. The aim of this study was to examine the clinical utility of these parameters in predicting extubation success. METHODS: This prospective study included 101 consecutive elderly patients undergoing a trial of extubation in the ICU of Haidian Hospital between June 2017 and July 2020. Patients were divided into the successful weaning group (n = 69) and the failed weaning group (n = 32). Baseline characteristics, including RSBI, were recorded. Measurements of DE, DTF and LUS were made using ultrasound within 24 h before extubation. RESULTS: Median DE was greater in patients with extubation success than in those with extubation failure (1.64 cm vs. 0.78 cm, p = 0.001). Patients with extubation success had a greater DTF than those with extubation failure (49.48% vs. 27.85%, p = 0.001). The areas under the receiver operating curves for the RSBI, LUS, DE and DFT were 0.680, 0.764, 0.831 and 0.881, respectively. The best cut-off values for predicting successful weaning were DTF ≥ 30%, DE ≥ 1.3 cm, LUS ≤ 11, and RSBI ≤ 102. The specificity of DTF (84%) in predicting weaning outcome was higher than that of RBSI (53%), that of LUS (55%), and that of DE (62%). The sensitivity of DTF (94%) was greater than that of RBSI (85%), that of LUS (71%), and that of DE (65%). The combination of RSBI, LUS, DE, and DTF showed the highest AUC (AUC = 0.919), with a sensitivity of 96% and a specificity of 89%. CONCLUSIONS: DTF has higher sensitivity and specificity for the prediction of successful weaning in elderly patients than the other parameters examined. The combination of RSBI, LUS, DE and DFT performed well in predicting weaning outcome. This has potentially important clinical application and merits further evaluation.

In vitro toxicological evaluation of a tobacco heating product THP COO and 3R4F research reference cigarette on human lung cancer cells.

Cigarette smoking increases health risks, such as respiratory diseases and heart diseases. Despite the decline in smoking rates in some countries, millions of adults still choose to smoke cigarettes. The use of next-generation nicotine delivery devices, such as tobacco heating products (THPs), may become a potentially safer alternative to smoking. Here, we report on the development of an electrically heated THP, coded as THP COO, with three different flavored tobacco sticks. The purpose of the study was to measure the levels of a list of harmful and potentially harmful constituents (HPHCs) in the total particulate matter (TPM) generated and to conduct a set of toxicological assessments of THP COO as compared with 3R4F reference cigarette. For all 55 HPHCs identified, the levels generated by the THP tobacco sticks were significantly lower in comparison to those in 3R4F TPM. The rate of reduction of HPHCs was between 68.6% and 99.9% under Health Canada Intense (HCI) smoking regimen. Human lung cancer cells (NCI-H292) exposed to 3R4F TPM showed dose-dependent responses for most of the 15 in vitro toxicity endpoints, whereas those exposed to comparable doses of THP COO TPMs did not. Therefore, exclusive use of the THP COO products may reduce the exposure of those tested HPHCs and thus potentially reduce health risk of smoking.

Deep learning for post-processing ensemble weather forecasts.

Quantifying uncertainty in weather forecasts is critical, especially for predicting extreme weather events. This is typically accomplished with ensemble prediction systems, which consist of many perturbed numerical weather simulations, or trajectories, run in parallel. These systems are associated with a high computational cost and often involve statistical post-processing steps to inexpensively improve their raw prediction qualities. We propose a mixed model that uses only a subset of the original weather trajectories combined with a post-processing step using deep neural networks. These enable the model to account for non-linear relationships that are not captured by current numerical models or post-processing methods. Applied to the global data, our mixed models achieve a relative improvement in ensemble forecast skill (CRPS) of over 14%. Furthermore, we demonstrate that the improvement is larger for extreme weather events on select case studies. We also show that our post-processing can use fewer trajectories to achieve comparable results to the full ensemble. By using fewer trajectories, the computational costs of an ensemble prediction system can be reduced, allowing it to run at higher resolution and produce more accurate forecasts. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Absorption and speciation of arsenic by microalgae under arsenic-copper Co-exposure.

Combined pollutions of arsenic (As) and copper (Cu) are common in water bodies near mines, non-ferrous metal smelting and power plants. This study investigated the effect of Cu(II) on the absorption and speciation of As(V) by microalgae. We compared the absorption and speciation of arsenic by microalgae (mainly Cyanophyta and Chlorophyta) when exposed to single As(V) with that exposed to As-Cu co-exposure in laboratory. The results showed that in the case of single As(V) exposure, the inhibitory effect of As(V) on microalgae was primarily affected by the exposure time, instead of the concentration of As(V) in the water solution. Compared with single As(V) exposure, the presence of Cu(II) under As-Cu co-exposure promoted the absorption and accumulation of As(V) by algae. The combination effect of As and Cu on algae was antagonistic instead of synergistic within the tolerance range of algae to them. In the presence of Cu(II), more monomethylarsonous acid (MMA) and dimethylarsinous acid (DMA), which are volatile organic arsenic compounds, were produced in algae compared with the control. The finding that Cu(II) can mediate the absorption and speciation processes of arsenic in algae has significance in possible bioremediation of arsenic pollution in aquatic environment.