[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

[Clinical update in non-invasive positive pressure ventilation for respiratory failure in 2022].

In this article, we searched the research literatures related to clinical investigation of non-invasive positive pressure ventilation (NPPV) in acute respiratory failure(ARF)/chronic respiratory failure(CRF) between 1st October 2021 and 30th September 2022 through Medline, and reviewed the important advances. Three prospective randomized controlled studies related to the efficacy and safety of NPPV and/or high-flow nasal cannula oxygen therapy (HFNC) on patients with COVID-19 with ARF were reported, showing that NPPV (including continuous positive airway pressure and bilevel positive airway pressure) was able to reduce the intubation rate, but the efficacy of HFNC was contradictory. In addition, progress has been made in outcome prediction models for ARF treated with NPPV, NPPV-related cardiac arrest, and the impact of human-machine interface on NPPV treatment outcomes. The effects of NPPV as preoxygenation method before intubation was reported to be able to reduce severe desaturation during intubation, especially in obese population. The use of NPPV in extubated patients resulting in reduced reintubation rate was also studied. With regard to long-term home application of NPPV, five indicators of successful initiation were proposed, but the success rate was low in clinical practice. Some reports showed that psychological support could improve the adherence to NPPV. The results of these studies contributed to the rational selection and optimal application of NPPV in clinical practice.

Influence of green light illumination at night on biological characteristics of the oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae).

The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.

Response of antioxidant enzymes in Mythimna separata (Lepidoptera: Noctuidae) exposed to thermal stress.

The oriental army worm Mythimna separata (Lepidoptera: Noctuidae) is a migratory pest in Eastern Asia and China. Seasonal high temperatures in Southern China and low temperatures in Northern China are pressures favouring the annual migration of this species, while cold tolerance determines the northern limit of its overwintering range. A number of physiological stress responses occur in insects as a result of variations in temperature. One reaction to thermal stress is the generation of reactive oxygen species (ROS), which can be harmful by causing oxidative damage. The time-related effects (durations of 1, 4 and 7 h) of thermal stress treatments of M. separata at comparatively low (5, 10, 15 and 20°C) and high (30, 35, 40 and 45°C) temperatures on the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POX) and glutathione S-transferases (GSTs), and total antioxidant capacity (T-AOC) were determined. Thermal stress resulted in significant elevation of the activities of SOD, CAT and GSTs, indicating that these enzymes contribute to defence mechanisms counteracting oxidative damage caused by an increase in ROS. However, at high-temperatures, POX and T-AOC were also found to contribute to scavenging ROS. Our results also indicate that extreme temperatures lead to elevated ROS production in M. separata. The present study confirms that thermal stress can be responsible for oxidative damage. To overcome such stress, antioxidant enzymes play key roles in diminishing oxidative damage in M. separata.

Alterations of Ca(v)1.2 and 5-hydroxytryptamine in rat hearts after positional asphyxia.

We investigated alterations of cardiac Ca(v)1.2 and 5-hydroxytryptamine (5-HT) associated with positional asphyxia. Male rats were divided into five groups: a control group with no restraint, group 1 restrained for 1 h, group 2 restrained for 2 h, group 3 restrained for 4 h, and group 4 restrained for 8 h. The rats that were restrained for 8 h ultimately suffered fatal asphyxia. After the restraint periods, the rats were sacrificed and immunohistochemistry was performed to evaluate the expressions of Ca(v)1.2 and 5-HT in the heart. Sections were analyzed by digital image analysis. Cardiac expression of Ca(v)1.2 and 5-HT proteins were significantly decreased by positional asphyxia in the rat, shown by integrated optical density (IOD) compared to controls. Our findings indicate that Ca(v)1.2 and 5-HT alterations could cause abnormal cardiac function, and the proteins investigated here may be useful for investigating the mechanisms underlying positional asphyxia.

Minocycline ameliorates hypoxia-induced blood-brain barrier damage by inhibition of HIF-1α through SIRT-3/PHD-2 degradation pathway.

BACKGROUND: Minocycline, a second-generation tetracycline alleviates neuro-inflammation and protects the blood-brain barrier (BBB) in ischemia stroke. However, the effect of minocycline in hypoxia-induced BBB damage is unclear. Here, we have investigated the effect of minocycline under hypoxia and explored its possible underlying mechanisms. METHODS: The effect of minocycline was examined in vitro in Human Brain Microvascular Endothelial Cells (HBMECs) using Trans Epithelial Electric Resistance (TEER). Protein and mRNA expression of Hypoxia-Inducible Factors-1α (HIF-1α), matrix metalloproteinases (MMP-2 and MMP-9) and tight junction proteins (TJs) were detected by using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The translocation and transcription of HIF-1α were detected by using immunocytochemistry and luciferase reporter assay. In vivo, to adult male Sprague Dawley (SD) rats under hypobaric hypoxia were administered minocycline for 1h and BBB permeability was tested by using Evans Blue and Transmission Electron Microscopy (TEM). Also, reduction of NAD-dependent deacetylase sirtuin-3 (SIRT-3)/proline hydroxylase-2 (PHD-2) signaling pathway was evaluated. RESULTS: Minocycline increased TEER in HBMECs after hypoxia (P<0.05), and reduced the extravasation of Evans Blue (P<0.05) and colloidal gold nanoparticles in rats. Minocycline administration significantly reduced HIF-1α expression, protein and mRNA expression of MMP-2, MMP-9 and Vascular Endothelial Growth Factor (VEGF) (P<0.05), and increased TJs (ZO-1, claudin-5 and occluding) (P<0.05) in HBMECs after hypoxia. Furthermore, minocycline reversed the hypoxia-induced reduction of PHD-2 (P<0.05) and SIRT-3 (P<0.05). Effects of minocycline were abolished by siRNA-mediated knockdown of SIRT-3 in the brain. CONCLUSIONS: Minocycline inhibits HIF-1α-mediated cellular responses and protects BBB integrity through SIRT-3/PHD-2 pathway, proving to be a potential drug for the prevention and treatment of hypoxic brain injuries.

Iterative ensemble Kalman filter for atmospheric dispersion in nuclear accidents: An application to Kincaid tracer experiment.

Information about atmospheric dispersion of radionuclides is vitally important for planning effective countermeasures during nuclear accidents. Results of dispersion models have high spatial and temporal resolutions, but they are not accurate enough due to the uncertain source term and the errors in meteorological data. Environmental measurements are more reliable, but they are scarce and unable to give forecasts. In this study, our newly proposed iterative ensemble Kalman filter (EnKF) data assimilation scheme is used to combine model results and environmental measurements. The system is thoroughly validated against the observations in the Kincaid tracer experiment. The initial first-guess emissions are assumed to be six magnitudes underestimated. The iterative EnKF system rapidly corrects the errors in the emission rate and wind data, thereby significantly improving the model results (>80% reduction of the normalized mean square error, r=0.71). Sensitivity tests are conducted to investigate the influence of meteorological parameters. The results indicate that the system is sensitive to boundary layer height. When the heights from the numerical weather prediction model are used, only 62.5% of reconstructed emission rates are within a factor two of the actual emissions. This increases to 87.5% when the heights derived from the on-site observations are used.

Modified ensemble Kalman filter for nuclear accident atmospheric dispersion: prediction improved and source estimated.

Atmospheric dispersion models play an important role in nuclear power plant accident management. A reliable estimation of radioactive material distribution in short range (about 50 km) is in urgent need for population sheltering and evacuation planning. However, the meteorological data and the source term which greatly influence the accuracy of the atmospheric dispersion models are usually poorly known at the early phase of the emergency. In this study, a modified ensemble Kalman filter data assimilation method in conjunction with a Lagrangian puff-model is proposed to simultaneously improve the model prediction and reconstruct the source terms for short range atmospheric dispersion using the off-site environmental monitoring data. Four main uncertainty parameters are considered: source release rate, plume rise height, wind speed and wind direction. Twin experiments show that the method effectively improves the predicted concentration distribution, and the temporal profiles of source release rate and plume rise height are also successfully reconstructed. Moreover, the time lag in the response of ensemble Kalman filter is shortened. The method proposed here can be a useful tool not only in the nuclear power plant accident emergency management but also in other similar situation where hazardous material is released into the atmosphere.

Comparative studies of zebrafish Danio rerio lipoprotein lipase (lpl) and hepatic lipase (lipc) genes belonging to the lipase gene family: evolution and expression pattern.

In this study, bioinformatics analysis, tissue distribution and developmental expression pattern of lipoprotein lipase (lpl) and hepatic lipase (lipc) in zebrafish Danio rerio are reported. In adult D. rerio, lpl was highly expressed in liver. This is remarkably different from the tissue expression pattern of LPL in mammals, which is not detected in the adult liver. The expression of lipc was liver specific, which is consistent with that in mammals. During embryogenesis, lpl mRNA was increased gradually in concentration from 0.5 hpf (hour post fertilization) to 6 dpf (days post fertilization), but lipc was not expressed at the early stage of the embryo until 3 dpf. In situ hybridization further displayed the expression pattern of lpl mainly restricted to the head region including cells surrounding the mouth opening, branchial arches, pectoral fin and lateral line neuromast, whereas lipc was mainly restricted to the liver and part of head regions including lens. This lays a foundation for further investigation of lpl or lipc function and evolution in fishes.

The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis.

BACKGROUND: Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial. METHODS: In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m(-2)) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication. RESULTS: Patients with higher BMI had more postoperative complication (P=0.002), such as anastomotic leakage (P=0.016) and cardiovascular diseases (P<0.001), but less incidence of chylous leakage (P=0.010). Logistic regression analysis showed that BMI (P=0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70-0.92, P=0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) (P<0.001), oesophageal adenocarcinoma (EA) (P=0.034), never-smoking (P=0.035), ever-smoking (P=0.035), never alcohol consumption (P=0.005), weight loss (P=0.003) and advanced pathological stage (P<0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02-1.06, P=0.001), wound infection (RR=1.03, 95% CI: 1.00-1.05, P=0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00-1.05, P=0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96-0.99, P<0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71-0.85, P<0.001). CONCLUSION: Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer.

Characterizations of particle size distribution of the droplets exhaled by sneeze.

This work focuses on the size distribution of sneeze droplets exhaled immediately at mouth. Twenty healthy subjects participated in the experiment and 44 sneezes were measured by using a laser particle size analyser. Two types of distributions are observed: unimodal and bimodal. For each sneeze, the droplets exhaled at different time in the sneeze duration have the same distribution characteristics with good time stability. The volume-based size distributions of sneeze droplets can be represented by a lognormal distribution function, and the relationship between the distribution parameters and the physiological characteristics of the subjects are studied by using linear regression analysis. The geometric mean of the droplet size of all the subjects is 360.1 µm for unimodal distribution and 74.4 µm for bimodal distribution with geometric standard deviations of 1.5 and 1.7, respectively. For the two peaks of the bimodal distribution, the geometric mean (the geometric standard deviation) is 386.2 µm (1.8) for peak 1 and 72.0 µm (1.5) for peak 2. The influences of the measurement method, the limitations of the instrument, the evaporation effects of the droplets, the differences of biological dynamic mechanism and characteristics between sneeze and other respiratory activities are also discussed.

Meta-analysis of association of common variants in the KCNJ11-ABCC8 region with type 2 diabetes.

KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) and ABCC8 (ATP-binding cassette, subfamily C (CFTR/MRP), member 8) have been studied for association with type 2 diabetes in various ethnic populations with contradictory results. We performed a comprehensive meta-analysis for KCNJ11 rs5219, rs5210, rs5215, and ABCC8 rs757110 to evaluate the effect of these regions on genetic susceptibility for type 2 diabetes. Forty-one case-control association studies of KCNJ11 and ABCC8 polymorphisms with type 2 diabetes, including 61,879 subjects, were identified and used in our meta-analysis. Combined odds ratios (OR) of associations of this disease with the rs5219 T, rs5210 G, rs5215 G, and rs757110 G alleles were 1.15 [95% confidence interval (95%CI) = 1.10-1.21, P < 0.0001], 1.16 (95%CI = 1.08-1.24, P = 0.023), 1.08 (95%CI = 1.02-1.13, P = 0.006), and 1.12 (95%CI = 1.07-1.18, P < 0.0001), respectively. The effect of allele T of rs5219 was similar (OR = 1.16) in Europeans and Japanese. However, rs5219 was not associated with type 2 diabetes in the Chinese Han population. Our meta-analysis demonstrated that KCNJ11 and ABCC8 polymorphisms are associated with risk for type 2 diabetes in the global population. Comparative genomics and bioinformatics analyses revealed that rs5210 is located within a conserved 3'-UTR, and that allele A may abolish the binding site of hsa-miR-1910 that the risk allele G possesses.

Lack of association of functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in the Chinese population based on a case-control study and a meta-analysis.

Uncoupling protein 2 (UCP2) is a mitochondrial transporter protein and can affect the function of ß-cells. We investigated a possible association between functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in 715 Hubei Han Chinese. No significant association was found, either for the -866G/A polymorphism (allele, P = 0.254; genotype, P = 0.508) or for the Ala55Val polymorphism (allele, P = 0.250; genotype, P = 0.896). Then, we reviewed the association of UCP2 -866G/A and Ala55Val polymorphisms with type 2 diabetes susceptibility in the Chinese population with a meta-analysis. Our meta-analysis, which included 3643 Chinese, further confirmed a lack of association of -866G/A and Ala55Val with type 2 diabetes (additive model: -866G/A, odds ratio = 1.09, 95% confidence interval = 0.94-1.27, P = 0.25; Ala55Val, odds ratio = 1.21, 95% confidence interval = 0.85-1.72, P = 0.28). Based on our case-control study and meta-analysis, we conclude that UCP2 Ala55Val and -866G/A polymorphisms are not significantly associated with type 2 diabetes risk in the Chinese population.

MicroRNA-217, down-regulated in clear cell renal cell carcinoma and associated with lower survival, suppresses cell proliferation and migration.

Aberrantly expressed microRNAs (miRNAs) are frequently correlated with a variety of human cancers, including clear cell renal cell carcinoma (ccRCC). In this study, we determined the expression patterns of miR-217 in ccRCC, and tested its effect on cancer cell proliferation and migration. The expression levels of miR-217 were determined in 54 ccRCC samples using Real-Time qPCR. 786-O and ACHN cells were transfected with miR-217 mimics or miRNA mimics control. Cell proliferation and migration were evaluated by MTT assay and scratch-wound assay, respectively. We found that miR-217 was down-regulated in ccRCC compared to paired normal tissue. Lower miR-217 expression levels were associated with higher tumor grade and stage. All patients with high miR-217 expression survived 5 years, while with low miR-217 expression, only 40% survived. Cell proliferation inhibition and decreased motility were observed in cells transfected with the miR-217 mimics. In conclusion, miR-217 plays a tumor suppressor role in ccRCC.

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese.

High-altitude pulmonary edema (HAPE) is a life-threatening condition caused by acute exposure to high altitude. Accumulating evidence suggests that genetic factors play an important role in the etiology of HAPE. However, conclusions from association studies have been hindered by limited sample size due to the rareness of this disease. It is known that mitochondria are critical for hypoxic adaptation, and mitochondrial malfunction can be an important factor in HAPE development. Therefore, we tested the hypothesis that mitochondrial DNA haplotypes and polymorphisms affect HAPE susceptibility. We recruited 204 HAPE patients and 174 healthy controls in Tibet (3658 m above sea level), all Han Chinese, constituting the largest sample size of all HAPE vulnerability studies. Among mtDNA haplogroups, we found that haplogroup D4 is associated with resistance to HAPE, while haplogroup B is a genetic risk factor for this condition. Haplogroup D4 (tagged by 3010A) may enhance the stability of 16S rRNA, resulting in reduced oxidative stress and protection against HAPE. Within haplogroup B, subhaplogroup B4c (tagged by 15436A and 1119C) was associated with increased risk for HAPE, while subhaplogroup B4b may protect against HAPE. We indicate that there are differences in HAPE susceptibility among mtDNA haplogroups. We conclude that mitochondria are involved in adverse reactions to acute hypoxic exposure; our finding of differences in susceptibility as a function of mitochondrial DNA haplotype may shed light on the pathogenesis of other disorders associated with hypoxia, such as chronic obstructive pulmonary disease.

CDKAL1 and type 2 diabetes: a global meta-analysis.

CDKAL1 (cyckin-dependent kinase 5 regulatory subunit-associated protein 1-like 1) has been shown to be associated with type 2 diabetes in various ethnic groups; however, contradictory results have been reported. We performed a comprehensive meta-analysis of 21 studies for rs7756992, 17 studies for rs7754840 and 10 studies for rs10946398 variants of the CDKAL1 gene to evaluate the effect of CDKAL1 on genetic susceptibility for type 2 diabetes. We found a significant association of rs7756992, rs7754840 and rs10946398 in CDKAL1 with type 2 diabetes (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.07-1.23, P < 0.0001; OR = 1.14, 95%CI = 1.06-1.24, P = 0.001, and OR = 1.12, 95%CI = 1.07-1.18, P < 0.0001, respectively). We conclude that there are significant associations between CDKAL1 polymorphisms and type 2 diabetes, but these associations vary in different ethnic populations.

Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.

SUMMARY: We performed an association study of five candidate genes within chromosome 3p14-25 in 1,080 Chinese female subjects. Polymorphisms in FLNB/CRTAP are associated with bone mineral density (BMD) in Chinese. INTRODUCTION: Chromosomal region 3p14-25 has shown strong evidence of linkage to BMD in genome-wide linkage scans. The variants responsible for this linkage signal, nonetheless, remain obscure. METHODS: Thirty SNPs in five positional and functional candidate genes within 3p14-25 (PPARG, CRTAP, TDGF1, PTHR1, and FLNB) and rs7646054 in the ARHGEF3 gene were genotyped in a case-control cohort of 1,080 Chinese females. Allelic and haplotypic association were tested using logistic regression analysis implemented in PLINK software. Potential transcription factor binding sites were predicted with MatInspector. RESULTS: Multiple SNPs and haplotypes in FLNB were significantly associated with BMDs, with the strongest association between lumbar spine BMD and rs9828717 (p = 0.005). SNP rs7623768 and the haplotype G-C of rs4076086-rs7623768 in CRTAP were associated with femoral neck BMD (p = 0.009 and p = 0.003, respectively). PTHR1 showed haplotypic associations with lumbar spine and femoral neck BMD (p = 0.02 and p = 0.044, respectively). Nevertheless, the association between rs7646054 in ARHGEF3 and BMD observed in Caucasians was not replicated in our samples. Comparative genomics analysis indicated that rs9828717 is located within a highly conserved region. The minor T allele at rs9828717 may lead to loss of binding site for nuclear factor of activated T cells which binds and triggers the transcriptional program of osteoblasts. CONCLUSIONS: Our data suggest that variants in FLNB and CRTAP at 3p are involved in BMD regulation in southern Chinese.

Genetic and environmental determinants of osteoporosis.

Osteoporosis is a common, complex disease that is influenced by genetic and environmental factors. Although molecular genetic studies have identified several potential regions of linkage, underlying susceptibility gene(s) are largely unknown. Genetic susceptibility to osteoporosis may be both context dependent and developmentally regulated, and epigenetic mechanisms are the likely link between gene and environment. In this paper we will review the status of genetic research into osteoporosis, and present the evidence for gene-environment interaction in its pathogenesis. Finally, the current challenges and future directions of research will be briefly discussed.