People are an organic unity: Gut-lung axis and pneumonia.

People are an organic unity. Every organ of our body doesn't exist alone. They are a part of our body and have important connections with other tissues or organs. The gut-lung axis is a typical example. Here, we reviewed the current research progress of the gut-lung axis. The main cross-talk between the intestine and lungs was sorted out, i.e. the specific interaction content contained in the gut-lung axis. We determine a relatively clear concept for the gut-lung axis, that is, the gut-lung axis is a cross-talk that the gut and lungs interact with each other through microorganisms and the immune system to achieve bidirectional regulation. The gut and lungs communicate with each other mainly through the immune system and symbiotic microbes, and these two pathways influence each other. The portal vein system and mesenteric lymphatics are the primary communication channels between the intestine and lungs. We also summarized the effects of pneumonia, including Coronavirus disease 2019 (COVID-19) and Community-Acquired Pneumonia (CAP), on intestinal microbes and immune function through the gut-lung axis, and discussed the mechanism of this effect. Finally, we explored the value of intestinal microbes and the gut-lung axis in the treatment of pneumonia through the effect of intestinal microbes on pneumonia.

Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons.

The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-stabilizing Arc 5'-untranslated-region RNA elements. These engineered EVs inherit endothelial adhesion molecules from donor leukocytes, recruit endogenous enveloping proteins to their surface, cross the BBB, and enter the neurons in neuro-inflammatory sites. Produced from self-derived donor leukocytes, the EVs are immunologically inert, and enhanced the neuronal uptake of the packaged mRNA in a mouse model of low-grade chronic neuro-inflammation.

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice.

OBJECTIVE: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. METHODS: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. RESULTS: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. CONCLUSION: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

Nonlinear association between self-reported sleep duration and cognitive function among middle-aged and older adults in China: The moderating effect of informal care.

BACKGROUND: Cognitive impairment is a major public health problem urgently to be solved. This study aims to examine the association between sleep duration and cognitive function and its two subdimensions: episodic memory and mental status, and to explore the moderating effects of informal care on these associations among middle-aged and older adults in China. METHODS: Data was drawn from China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, 2015 and 2018 datasets. Sleep duration and informal care were self-reported. Cognitive function was measured using CHARLS Harmonized Cognitive Assessment Protocol. Effects of informal care on sleep duration-cognitive function were assessed using Generalized Estimating Equations models. RESULTS: The relationships between sleep duration and cognitive function, episodic memory, and mental status were all found to follow an inverted U-shaped pattern. Spouse care weakened the adverse effects of extreme sleep duration on cognitive function while the children care amplified them. Further, we only observed the moderating effects of spouse and children care on the association between sleep duration and episodic memory, but not mental status. CONCLUSIONS: The relationships between sleep duration and cognitive function, along with its different dimensions, are nonlinear in nature. The impacts of sleep duration on cognitive function and its dimensions are contingent upon the levels of informal care received and the sources of that care. We provide valuable insights into the complex interplay between sleep duration, informal care, and cognitive function.

Lianhua Qingke Preserves Mucociliary Clearance in Rat with Acute Exacerbation of Chronic Obstructive Pulmonary Disease by Maintaining Ciliated Cells Proportion and Protecting Structural Integrity and Beat Function of Cilia.

Purpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD. Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 µg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and ß-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera. Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF. Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.

Therapeutic potential of Lianhua Qingke in airway mucus hypersecretion of acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Lianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 µg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed. RESULTS: LHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation. CONCLUSION: LHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD.

Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.

Large eddy simulation on wind-induced interference effects of staggered chamfered square cylinders.

Chamfered corners in buildings are the main means to reduce the control effect of wind load on the structure, and the interference effect of chamfered buildings cannot be ignored. At present, only the mutual interference coefficients of square and rectangular section buildings are given in the Chinese code, without the interference effect of chamfered buildings being specified. Therefore, in this paper, aerodynamic force and wind pressure coefficients of chamfered square cylinders of different spacing are obtained by the large eddy simulation method. Wind load characteristics, non-Gaussian characteristics and interference effects of chamfered square cylinders with different arrangements are studied based on aerodynamic coefficients, wind pressure coefficients and interference coefficients. The results show that when the wall y plus value is 1, the large eddy simulation is the most accurate to simulate the wind load and wind field parameters. Besides, the aerodynamic effects, non-Gaussian characteristics and interference effects between the chamfered square cylinders are mainly controlled by the cross-wind interval and the spacing (4.0, 4.0) is the characteristic coordinate. That means, when the spacing is smaller than this coordinate, the interference effect of the square cylinder is more obvious. When the spacing coordinate is greater than (4.0, 4.0), the aerodynamic coefficients and non-Gaussian regional distributions of the principal square cylinder and the isolated cylinder are the same, and the interference factor approaches 1.

Tongxinluo enhances the effect of atorvastatin on the treatment of atherosclerosis with chronic obstructive pulmonary disease by maintaining the pulmonary microvascular barrier.

Atherosclerosis (AS) is a common comorbidity of chronic obstructive pulmonary disease (COPD), and systemic inflammation is an important mechanism of COPD with AS. Tongxinluo (TXL) improves the function of vascular endothelial cells. We aimed to prove that impairment of pulmonary microvascular barrier function is involved in COPD-mediated aggravation of AS and investigate whether TXL enhances the effect of Ato (atorvastatin) on COPD with AS by protecting pulmonary microvascular endothelial barrier function. In vivo, a COPD with atherosclerotic apolipoprotein E knockout (AS ApoE-/-) mouse model was established by cigarette smoke combined with a high-fat diet. The animals were administered TXL, Ato, and TXL + Ato once a day for 20 weeks. Lung function, lung microvascular permeability, lung inflammation, systemic inflammation, serum lipid levels, atheromatous plaque formation, and endothelial damage biomarkers were measured. In vitro, human pulmonary microvascular endothelial cells (HPMECs) were pretreated with TXL and incubated with cigarette smoke extract to establish the model. The permeability of the endothelial monolayer, inflammatory cytokines, endothelial damage biomarkers, and tight junction (Tj) proteins were determined. Cigarette smoking significantly exacerbated the high-fat diet-induced pulmonary function decline, pulmonary microvascular endothelial barrier dysfunction, inflammation, and atherosclerotic plaques. These changes were reversed by TXL-Ato; the combination was more effective than Ato alone. Furthermore, TXL protected the HPMEC barrier and inhibited inflammation in HPMECs. COPD aggravates AS, possibly through the destruction of pulmonary microvascular barrier function; thus, lung inflammation triggers systemic inflammation. In treating COPD with AS, TXL enhances the antiatherosclerotic effect of Ato, protecting the pulmonary microvascular barrier.

Effect of Astragalus injection on inflammatory mediators in patients with viral myocarditis: A systematic review and meta-analysis.

BACKGROUND: To explore the therapeutic effect and mechanism of Astragalus injection on viral myocarditis, we conducted a systematic review and meta-analysis to identify the influence of Astragalus injection on inflammatory mediators and overall efficiency in patients undergoing viral myocarditis. METHODS: EMBASE, Cochrane Library, PubMed, Chinese Biomedical Literature, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched to screen randomized controlled trials (RCTs) published before July 3, 2022. The quality of participating studies was assessed by the Cochrane Collaboration Risk of Bias tool. The calculation of qualitative data used a risk ratio (RR) with a 95% confidence interval (95% CI), and quantitative data had standardized mean differences (SMDs) with a 95% CI. The heterogeneity among trials was quantified with Cochran's Q test and the I2 statistic. Confounding factors were estimated by sensitivity analysis, meta-regression, and subgroup analysis. The publication bias of participating articles was evaluated by funnel plot and Egger's test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was recommended for assessing the strength of evidence. RESULTS: Nineteen available studies were included in our present meta-analysis, all of which were conducted in China. The outcomes expose that Astragalus injection dramatically decreased the levels of pro-inflammatory TNF-α (SMD=-2.271, 95% CI=-2.802 to -1.739, p<0.001, I2=90.6%), IL-6 (SMD=-1.501, 95% CI=-1.872 to -1.130, p<0.001, I2=83.2%), IL-17 (SMD=-3.194, 95% CI=-4.569 to -1.818, p<0.001, I2=88.9%), 1L-8 (SMD=-6.133, 95% CI=-9.938 to -2.328, p = 0.002, I2=97%), 1L-1 (SMD=-1.814, 95% CI=-2.557 to -1.070, p<0.001, I2=92.1%), CRP (SMD=-2.020, 95% CI=-3.107 to -0.932, p<0.001, I2=92.7%), and IFN-γ (SMD=-1.512, 95% CI=-2.771 to -0.253, p = 0.019, I2=92%) and increased the total effective rate of treatment (RR=1.225, 95% CI=1.17 to 1.29, p<0.001, I2=0.0%) in patients with viral myocarditis. CONCLUSION: Astragalus injection can play a therapeutic role in patients with viral myocarditis through immunomodulatory effects. Outcomes were treated with caution due to significant heterogeneity among studies. Large-scale RCTs should be performed to support these conclusions.

N-Acetylcysteine alleviates high fat diet-induced hepatic steatosis and liver injury via regulating the intestinal microecology in mice.

N-Acetylcysteine (NAC), a well-accepted antioxidant, has been shown to protect against high fat diet (HFD)-induced obesity-associated non-alcoholic fatty liver disease (NAFLD) in mice. However, the underlying mechanism(s) of the beneficial role of NAC is still not fully understood. Our study aimed to evaluate the protective effect of NAC against NAFLD in terms of gut microbiota homeostasis. Thirty-two C57BL/6 mice were divided into four groups, including chow diet (CHOW), high-fat diet (HFD), CHOW + NAC (2 g L-1 in the drinking water), and HFD + NAC groups, and fed for 12 weeks. NAC supplementation significantly improved HFD-induced obesity, dyslipidemia, and liver dysfunction in mice. NAC also rescued HFD-caused disorder of the gut microbiota. Intriguingly, removing intestinal microorganisms by antibiotics (ABX) obviously abolished NAC supplementation-rescued hepatic steatosis and liver injury, indicating the involvement of the gut microbiota in the beneficial role of NAC. The profiles of 1145 expressed hepatic mRNAs were analyzed by whole transcriptome sequencing. Among those, 5 up-expressed mRNAs induced by a HFD, including Cidea, CD36, Acnat2, Mogat1, and GPAT3, were reversed by NAC treatment, which was further verified by a quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, those 5 mRNAs exhibited a significant (negative or positive) association with bacterial phyla or genera, including phyla Firmicutes and Bacteroidetes and genera norank_f_Erysipelotrichaceae and Lachnoclostridium, by Spearman's correlation analysis. These results suggested that the homeostasis of the gut microbiota plays an important role in NAC-improved NAFLD by affecting the enterohepatic axis.

Tongxinluo prevents chronic obstructive pulmonary disease complicated with atherosclerosis by inhibiting ferroptosis and protecting against pulmonary microvascular barrier dysfunction.

Cardiovascular comorbidities are pervasive in chronic obstructive pulmonary disease (COPD) and often result in serious adverse cardiovascular events. Tongxinluo (TXL) has been clinically verified to treat atherosclerosis (AS), improve lung function and alleviate dyspnoea. The present study aimed to explore the effect of lung microvascular barrier dysfunction on AS in COPD and the potential pulmonary protective mechanisms of TXL in COPD complicated with AS. COPD complicated with AS was induced in mice by cigarette smoke (CS) exposure and high-fat diet (HFD) feeding. The mice were treated with atorvastatin (ATO), TXL or combination therapy (ATO+TXL) for 20 weeks. Pulmonary function, lung pathology, serum lipid levels, atherosclerotic plaque area and indicators of barrier function, oxidative stress and ferroptosis in lung tissue were evaluated. In vitro, human pulmonary microvascular endothelial cells (HPMECs) were pretreated with TXL for 4 h and then incubated with cigarette smoke extract (CSE) and homocysteine (Hcy) for 36 h to induce barrier dysfunction. Then the indicators of barrier function, oxidative stress and ferroptosis were measured. The results demonstrate that CS aggravated dyslipidaemia, atherosclerotic plaque formation, pulmonary function decline, pathological injury, barrier dysfunction, oxidative stress and ferroptosis in the HFD-fed mice. However, these abnormalities were partially reversed by ATO and TXL. Similar results were observed in vitro. In conclusion, pulmonary microvascular barrier dysfunction plays an important role by which COPD affects the progression of AS, and ferroptosis may be involved. Moreover, TXL delays the progression of AS and reduces cardiovascular events by protecting the pulmonary microvascular barrier and inhibiting ferroptosis.

Evaluation of nutrition status of very preterm infants in neonatal intensive care units using different growth indicators.

BACKGROUND:  Nutrition status of very preterm infants in the neonatal intensive care unit (NICU) is strongly associated with postnatal growth. This study aimed to develop indicators of nutrition status using growth data of very preterm infants during hospitalization. METHODS: The data of 596 newborns from eight NICUs were retrospectively analyzed. Inclusion criteria were birth at <32 weeks' gestation, NICU admission ≤24 h after delivery, and length of hospital stay ≥28 days. Three indicators were evaluated: (indicator I) prevalence of extrauterine growth restriction (EUGR); (indicator II) z-score for change in weight from birth to discharge, adjusted for birth weight z-score and gestational age; and (indicator III) change in weight z-score from birth to discharge, adjusted for birth weight z-score, gestational age, and time to regain birth weight. Using data from NICU 1 as the reference for the latter two indicators, we established linear regression models of the adjusted change in weight z-score from birth to discharge. The difference between the observed value and the baseline value (calculated by the two models) served as the nutrition indices. RESULTS: The prevalence of EUGR differed significantly between the eight NICUs (P = .009). Statistically significant differences were found between the mean indices calculated by the other two models (all P < .05). CONCLUSIONS: Indicator III, change in weight z-score from birth to discharge (adjusted for birth weight z-score, gestational age, and time to regain birth weight), appears to be the most accurate for evaluating the quality of nutrition in the NICU.

Dual catalytic cascaded nanoplatform for photo/chemodynamic/starvation synergistic therapy.

In this study, manganese dioxide (MnO2) was attached to prussian blue (PB) by a one-pot method to prepare PBMO. Then, the GOD was loaded onto PBMO through the electrostatic interaction of hyaluronic acid (HA) to form tumor-targeted nanoplatform (PBMO-GH). Hydrogen peroxide (H2O2) and gluconic acid were produced through the GOD-catalyzed enzymatic reaction. Meanwhile, PB could not only catalyze H2O2 for oxygen generation to further promote glucose consumption but also possess the property of photothermal conversion. As a result, glucose was continuously consumed to achieve the starvation therapy (ST), and the photothermal therapy (PTT) could be realized under near-infrared (NIR) light. Besides, the Mn2+ generated by the reaction of MnO2 with glutathione (GSH) could exert Fenton-like reaction to produce highly toxic hydroxyl radicals (·OH) from H2O2, which thereby realized self-reinforcing chemodynamic therapy (CDT). In vitro and in vivo experiments demonstrated that PBMO-GH could effectively inhibit the growth of tumor cells via ST/CDT/PTT synergistic effect. Therefore, the as-prepared nanoplatform for multi-modal therapy will provide a promising paradigm for overcoming cancer.

Enhanced antitumor effect via amplified oxidative stress by near-infrared light-responsive and folate-targeted nanoplatform.

The efficiency of producing hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) catalyzed by different iron compounds have been explored extensively. Exclusively, ferrocenecarboxylic acid (FCA) showed the best catalyzed activity for ·OH generation. Then, we designed and prepared near-infrared (NIR) light-responsive and folate-targeted nanoplatform, which co-delivered FCA, cisplatin and indocyanine green (ICG) for improving antitumor therapy through amplified oxidative stress. The noteworthy observation is that under the irradiation of NIR light, the lecithin structure could able to depolymerize through the photothermal conversion mechanism of encapsulated dye ICG, which has achieved an intelligent release of drugs. In addition, the released cisplatin is not only fully effective to damage the DNA of cancer cells but it is able to induce the production of intracellular H2O2, which could further be catalyzed by FCA to generate toxic ·OH for oxidative damage via Fenton and Haber-Weiss reaction. This original strategy may provide an efficient way for improved chemotherapy via amplified oxidative stress.

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

[An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China].

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS: Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.

Costs of hospitalization for stroke from two urban health insurance claims data in Guangzhou City, southern China.

BACKGROUND: Stroke remains a major global health problem. In China, stroke was the leading cause of death and imposed a large impact on the healthcare system. This study aimed to examine the hospitalization costs by five stroke types and the associated factors for inpatient costs of stroke in Guangzhou City, Southern China. METHODS: This was a prevalence-based, cross-sectional study. Data were obtained from urban health insurance claims database of Guangzhou city. Samples including all the reimbursement claims submitted for inpatient care with the primary diagnosis of stroke from 2006 to 2013 were identified using the International Classification of Diseases codes. Descriptive analysis and multivariate regression analysis based on the Extended Estimating Equations model were performed. RESULTS: A total of 114,872 hospitalizations for five stroke types were identified. The average age was 71.7 years old, 54.2% were male and 60.1% received medical treatment in the tertiary hospitals, and 92.3% were covered by the urban employee-based medical insurance. The average length of stay was 26.7 days. Among all the hospitalizations (average cost: Chinese Yuan (CNY) 20,203.1 = $3212.1), the average costs of ischaemic stroke (IS), subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH), transient ischaemic attack (TIA), and other strokes were CNY 17,730.5, CNY 62,494.2, CNY 38,757.6, CNY 10,365.3 and CNY 18,920.6, respectively. Medication costs accounted for 42.9, 43.0 and 40.4% of the total inpatient costs among patients with IS, ICH and TIA, respectively, whereas for patients with SAH, the biggest proportion of total inpatient costs was from non-medication treatment costs (57.6%). Factors significantly associated with costs were stroke types, insurance types, age, comorbidities, severity of disease, length of stay and hospital levels. SAH was linked with the highest inpatient costs, followed by ICH, IS, other strokes and TIA. CONCLUSIONS: The costs of hospitalization for stroke were high and differed substantially by types of stroke. These findings could provide economic evidence for evaluating the cost-effectiveness of interventions for the treatment of different stroke types as well as useful information for healthcare policy in China.

Costs of Hospitalization for Dementia in Urban China: Estimates from Two Urban Health Insurance Scheme Claims Data in Guangzhou City.

Background: Dementia is one of the public health priorities in China. This study aimed to examine the hospitalization costs of patients with dementia and analyzed the factors associated with their inpatient costs. Methods: This was a prevalence-based, observational study using claims data derived from two urban insurance schemes during the period from 2008 through 2013 in Guangzhou. The extended estimating equations model was performed to identify the main drivers of total inpatient costs. Results: We identified 5747 dementia patients with an average age of 77.4. The average length of stay (LOS) was 24.2 days. The average hospitalization costs per inpatient was Chinese Yuan (CNY) 9169.0 (CNY 9169.0 = US$1479.8 in 2013). The mean inpatient costs for dementia patients with the Urban Employee-based Basic Medical Insurance (UEBMI) scheme (CNY 9425.0 = US$1521.1) were higher than those for patients with the Urban Resident-based Basic Medical Insurance scheme (CNY 7420.5 = US$1197.6) (p < 0.001). Having UEBMI coverage, dementia subtypes, having hypertension, being admitted in larger hospitals, and longer LOS were significantly associated with hospitalization costs of dementia. Conclusions: The costs of hospitalization for dementia were high and differed by types of insurance schemes. Dementia was associated with substantial hospitalization costs, mainly driven by insurance type and long LOS. These findings provided economic evidence for evaluating the burden of dementia in China.