Global, regional, and national burden of chronic respiratory diseases and associated risk factors, 1990-2019: Results from the Global Burden of Disease Study 2019.

Background: The burden of chronic respiratory diseases has changed over the three decades. This study aims to describe the spatiotemporal trends of prevalence, mortality, and disability-adjusted life years (DALY) due to chronic respiratory diseases (CRDs) worldwide during 1990-2019 using data from the Global Burden of Disease Study 2019 (GBD 2019). Methods: The prevalence, mortality, and DALY attributable to CRDs and risk factors from 1990 to 2019 were estimated. We also assessed the driving factors and potentiality for improvement with decomposition and frontier analyses, respectively. Results: In 2019, 454.56 [95% uncertainty interval (UI): 417.35-499.14] million individuals worldwide had a CRD, showing a 39·8% increase compared with 1990. Deaths due to CRDs were 3.97 (95%UI: 3.58-4.30) million, and DALY in 2019 was 103.53 (95%UI: 94.79-112.27) million. Declines by average annual percent change (AAPC) were observed in age-standardized prevalence rates (ASPR) (0.64% decrease), age-standardized mortality rates (ASMR) (1.92%), and age-standardized DALY rates (ASDR) (1.72%) globally and in 5 socio-demographic index (SDI) regions. Decomposition analyses represented that the increase in overall CRDs DALY was driven by aging and population growth. However, chronic obstructive pulmonary disease (COPD) was the leading driver of increased DALY worldwide. Frontier analyses witnessed significant improvement opportunities at all levels of the development spectrum. Smoking remained a leading risk factor (RF) for mortality and DALY, although it showed a downward trend. Air pollution, a growing factor especially in relatively low SDI regions, deserves our attention. Conclusion: Our study clarified that CRDs remain the leading causes of prevalence, mortality, and DALY worldwide, with growth in absolute numbers but declines in several age-standardized estimators since 1990. The estimated contribution of risk factors to mortality and DALY demands the need for urgent measures to improve them. Systematic review registration: http://ghdx.healthdata.org/gbd-results-tool.

Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism.

BACKGROUND AND OBJECTIVE: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. METHODS: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. RESULTS: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid- and long-term mortalities (p <0.05). By including hypocalcaemia, the new 30-day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well-performing predictive validity was also verified on a constructed external validation cohort. CONCLUSION: Hypocalcaemia is independently associated with mid- and long-term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE.

[Removal of Phosphate by Calcite in Open-System].

Batch methods were deployed to study the removal of phosphate by calcite in an open-system. Results showed that: (1) The pre-equilibrium process of calcite in open system could be achieved within 24 hours (2) The kinetic results showed that, at initial concentration of 0.5 mg · L⁻¹, the phosphate removal was almost completed within 10 hours of the first phase. The observation may be attributed to surface adsorption. At initial concentration of 2.5 mg · L⁻¹, the phosphate removal was mainly carried out by the precipitation of phosphate at later stage of the process; (3) At initial concentration of ≤ 2.5 mg · L⁻¹ setting 10 h as reaction time, the phosphate removal process was described well by the Langmuir model. It is hypothesized that surface adsorption was the principal removal way of phosphate; (4) With the addition of phthalate, at initial concentration of < 2.5 mg · L⁻¹, the phosphate removal rate experienced a small decrease. That was because phosphate was mainly removed by surface adsorption, and thus, phthalate was a competitor to phosphate for the same adsorption site. The phosphate removal rate increased a little at initial concentration of > 2.5 mg · L⁻¹, this was because the phosphate precipitation was reinforced by the increase of calcium concentration, which was caused by phthalate addition.

Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells.

The objective was to investigate the molecular mechanism of mitochondrial reactive oxygen species (ROS) signaling regulation of pulmonary artery endothelial cell (HPAEC) secretion in the condition of oxidative stress. Acrolein (40 µM) induced HPAEC mitochondrial generation of ROS, rotenone (2 µmol/L) blocked mitochondrial respiratory chain complex I, cesium chloride (CsCl, 40 mmol/L)blocked K(+)channels, and saline (0.9 g/dl) were used as control. The generations of NOS, ET-1 and VEGF were determined with ELISA in the condition of different treatment reagents namely acrolein, acrolein plus rotenone, acrolein plus CsCl and saline. In the different reagent treatment of HPAECs, acrolein increased mitochondrial ROS, membrane potential, Kv1.5 mRNA and protein expression, intracellular calcium and the generation of NOS (determining NO production), ET-1 and VEGF, and those were reduced by rotenone. CsCl decreased the increment of membrane potential, the elevation of intracellular calcium and the upregulation of NOS, E-1 and VEGF expressions, which were induced by acrolein. The present study demonstrated that mitochondrial ROS-K(+)channel regulated HPAEC secretion of NO, ET-1 and VEGF in the condition of oxidative stress. Kv1.5 channel may be an important component of ROS-K+ channel signaling pathway, and intracellular calcium contributed to mitochondrial ROS-K(+) channel signaling modulation of HPAEC secretion.

Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected. RESULTS: The mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05). CONCLUSIONS: The results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.

[The effects of safflower injection on lipid peroxidation level and expression of heme oxygenase-1 of the rat liver with hypoxia and hypercapnia].

AIM: To investigate the changes of lipid peroxidation level and expression of heme oxygenase-1 of the rat liver with chronic hypoxia and hypercapnia, and the effects of Safflower injection (a compond of Chinese Traditional medicine). METHODS: Thirty male SD rats weighing 180 approximately 220 g were divided into three groups (n=10): control group (N group), chronic hypoxia and hypercapnia for four weeks group(F group), and Safflower injection group (H group). SOD and MDA in liver tissue were measured by spectrophotometric method. And methods Immunohistochemical assay was used to detect the distribution of HO-1 protein. Pathological changes in liver tissues were observed in HE staining section. The mRNA expressions of HO-1 in liver were detected by semi-quantitative RT-PCR. RESULTS: The activity of SOD of the liver in F group were significantly lower than those in N group, and the content of MDA were significantly higher. The activity of SOD of the liver in H group were significantly higher than those in F group, and the content of MDA were significantly lower. In F group there were multiple dispersed immunoreactivity cells in liver. And compared to those in F group, the immunoreactivity cells were significantly decreased in H group. HE staining revealed that there were many hepatocytes with obvious adipose degeneration. Hepatic pathological damage in H group was slighter than that in F group. The expression of HO-1 mRNA of the liver in F group were significantly higher than those in N group (P < 0.01), and those in H group were significantly lower than those in F group (P < 0.01) . CONCLUSION: Chronic hypoxia and hypercapnia increases the level of oxidative stress. Safflower injection have a protective effect, maybe because of the accommodation of the expression of HO-1 of the liver and the elimination of free radicals.

[Diagnostic value of DNA, RNA and proliferating cell nuclear antigen examination in malignant pleural effusions by flow cytometry].

OBJECTIVE: To study the diagnostic value of DNA, RNA and proliferating cell nuclear antigen (PCNA) examination in malignant effusion by multiparametric flow cytometry, and therefore to provide proof for clinical application. METHODS: Forty seven patients with pleural effusions in our hospital from August 2003 to February 2004 were divided into two groups: 19 suffering from benign pleural effusions and 28 from malignant effusions confirmed by pathologic examination. The cells for diagnosis were divided into four groups stained by PI (Propidium-iodide), PY (Pyronin), PCNA-FITC and PCNA-mouse-alpha-2a. The specimens were analyzed by a flow cytometer (FacS Caliber, Becton Dickinson). The sensitivity and the specificity of each examination and combined examination were calculated by statistic software SPSS 13.0. RESULTS: (1) The expression of DI, RI, and PI in benign pleural effusion was 1.03 +/- 0.06, 10.03 +/- 0.54, and (4.86 +/- 0.72)%, respectively, and those in malignant ones was 1.26 +/- 0.17, 11.65 +/- 1.45, and (11.97 +/- 1.50)%, respectively, the difference being statistically significant. The cutoff value of DI, RI and PI was 1.10%, 10.75% and 4.56%, and the sensitivity of DI examination was 89.3%, 78.6%, 75.0%, and the specificity was 89.5%, 98.5%, 84.2%, respectively. (2) In 6 cases suffering from malignant pleural effusions, RI was positive but DI was negative, indicating that DI combined with RI examination was better than DI examination alone. (3) In 5 cases suffering from malignant pleural effusions confirmed by tissue examination, the cytology was negative, but the result of DI and RI was abnormal, indicating that flow cytometry was complementary to pathologic examination. (4) The sensitivity of DI + RI, DI + PI, RI + PI and DI + RI + PI combined examination was 98.2%, 89.3%, 89.3%, 92.9%; the specificity was 84.2%, 89.5%, 84.2%, 94.2% respectively. The results demonstrated that DI + RI + PI combined examination was the best, which showed the least false negative and false positive results. The sensitivity of DI + RI combined examination was 98.2%, but the specificity was 84.2%, the false positive rate being higher than DI + RI + PI combined examination. In none of the benign pleural effusions was the DI + RI + PI higher than the cutoff value, suggesting that combined examination can exclude benign pleural effusions. CONCLUSIONS: DNA, RNA and PCNA examinations by flow cytometry are of value in the diagnosis of malignant effusion, especially for cases which can not be diagnosed by cytological examination. DI + RI + PI combined examination showed better results with the lowest false negative and false positive rates.

[An experimental study on the regulation of pulmonary arterial remodeling by protein kinase C in chronic hypoxic rats].

AIM: To investigate the effect of protein kinase C regulating pulmonary arterial remodeling in chronic hypoxic rats. METHODS: Electron microscope, radioactivity, immunohistochemistry and image analyser were used. RESULTS: (1) Mean pulmonary arterial pressure (mPAP) and weight ratio of RV to LV + S were significantly higher than that of control group (P < 0.01). (2) WA/TA and SMC were significantly higher than that of control group (P < 0.01). Electron microscopy showed the proliferation of smooth muscle cells and the disposition of collagenous fiber in pulmonary arterioles induced by hypoxia. (3) The total, cytosolic, particulate fraction PKC activity and the ratio of particulate fraction to total PKC activity were significantly higher than that of control group (P < 0.01). (4) Expression of PKC, collagen I were significantly higher than that of control group (P < 0.01), the difference of collagen III was not significant between two groups (P > 0.05). (5) There were good correlation between the total, particulate fraction PKC activity, the ratio of particulate fraction to total PKC activity, expression of PKC and SMC, collagen I in pulmonary arterioles. CONCLUSION: The PKC regulates the proliferation of pulmonary artery smooth muscle cells and expression of pulmonary arterial collagen in chronic hypoxic rats, which may play an important role in the pathogenesis of pulmonary hypertension and structural remodeling of pulmonary arteries.