pH-Responsive injectable self-healing hydrogels loading Au nanoparticles-decorated bimetallic organic frameworks for synergistic sonodynamic-chemodynamic-starvation-chemo therapy of cancer.

A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O2) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O2 into singlet oxygen (1O2) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies.

Omnidirectional and near-unity nonreciprocal thermal radiation with trilayer cavities-enhanced approach.

From the standpoint of thermal radiation, omnidirectional nonreciprocal thermal radiation (NTR) is strongly desired for thermal energy harvesting. Here, we propose theoretically lithographic free thermal emitter made in a dielectric-Weyl semimetal (WSM)-dielectric fashion and terminated by a metallic substrate. By engineering the structural parameters, a surprising result of spectrally selective as well as omnidirectional (along both polar and azimuthal angles) NTR is realized. It is shown that the magnitude and sign of the contrast between emission (e) and absorption (α) can be managed simultaneously. The suggested structure shows good nonreciprocity stability in a wide range of polar and azimuthal angles for transverse magnetic (TM) polarized incident wave. The ability to fine tune nonreciprocal radiative properties of our design suggests a relatively simple way to manifest the NTR with high performance, which could lead to the development of power scavenging and conversion devices.

IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes.

Investigating correlations between radiomic and genomic profiling in breast cancer (BC) molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment. We present a well-designed radiogenomic framework image-gene-gene set (IMAGGS), which detects multi-way associations in BC subtypes by integrating radiomic and genomic features. Our dataset consists of 721 patients, each of whom has 12 ultrasound (US) images captured from different angles and gene mutation data. To better characterize tumor traits, 12 multi-angle US images are fused using two distinct strategies. Then, we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm, deviating from the prevalent one-to-one relationship pattern observed in previous studies. Key radiomic and genomic features are screened using these associations. In addition, gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC subtypes. We further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and diseases. Taken together, IMAGGS provides a comprehensive characterization for diseases by associating imaging, genes, and gene sets, paving the way for biological interpretation of radiomics and development of targeted therapy.

A pH-responsive supramolecular hydrogel encapsulating a CuMnS nanoenzyme catalyst for synergistic photothermal-photodynamic-chemodynamic therapy of tumours.

Traditional cancer therapies no longer meet the current demand for cancer precision therapy and personalized treatment and it's essential to develop new therapeutic modalities as well as to investigate new combination anti-tumor mechanisms. Therefore, amphiphilic prodrug polymer chains linking methoxy poly(ethylene glycol) (mPEG) and cinnamaldehyde (CA) with adipic acid dihydrazide (ADH) as the pH-responsive center were designed and synthesized, which could self-assemble into PAC micelles in aqueous solution. A supramolecular hydrogel was formed based on the host-guest interaction between α-cyclodextrin (α-CD) and PAC micelles. Polyetherimide (PEI) modified copper manganese sulfide nanoenzyme catalysts (PCMS NPs) were prepared by a solvothermal method, which could be uniformly dispersed in the hydrogel to form a composite supramolecular hydrogel (PCMS@PAC/α-CD Gel). Under an acidic tumor environment, pH-responsive hydrazone bonds were broken, resulting in the slow release of CA and the amplification of hydrogen peroxide (H2O2) levels. PCMS NPs exerted peroxidase (POD)-like activity and catalase (CAT)-like activity, which could convert H2O2 into hydroxyl radicals (˙OH) and oxygen (O2) to alleviate intra-tumor hypoxia and induce apoptosis, while exerting glutathione oxidase (GPX)-like activity to consume glutathione (GSH) to further enhance the effect of chemodynamic therapy (CDT). Under near-infrared light (NIR) irradiation, PCMS NPs exhibited an excellent photothermal conversion performance, which could rapidly increase the temperature of tumor cells to above 42 °C for photothermal therapy (PTT) and convert O2 to a superoxide anion (˙O2-) by exerting oxidase (OXD)-like activity for photodynamic therapy (PDT). It was demonstrated by in vitro and in vivo experiments that the PCMS@PAC/α-CD Gel was highly cytotoxic to cancer cells and could effectively inhibit tumor growth, indicating the potential for applications in the fields of biomedicine and smart materials.

[Diagnostic yield of bronchoscopic rapid on-site evaluation in severe invasive bronchopulmonary aspergillosis].

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS: Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.

Weyl semimetal mediated epsilon-near-zero hybrid polaritons and the induced nonreciprocal radiation.

Polaritonic excitation and management in ultra-thin polar crystals has recently received significant attention and holds new promise for epsilon-near-zero (ENZ) modes. However, manipulation of the ENZ mode via anisotropic magneto-optic (MO) material remains elusive. Herein, we provide an effective strategy for constructing an ENZ polar thin film with dependence on Weyl semimetals (WSM). The thermal radiation of the proposed device is explored with electromagnetic (EM) simulations that utilize the anisotropic rigorous coupled-wave analysis (aRCWA) method. Strong coupling of the ENZ mode to WSM polaritons has been demonstrated, and the structural parameters hold tolerance on the order of hundreds of nanometers, which is highly favorable for low-cost fabrication and high-performance application. By changing both the azimuthal angle (ϕ) and angle of incidence (θ), the nonreciprocity (η) can be effectively influenced. The distribution of η is symmetrical with ϕ = 180°, η = 0 when ϕ = 90° and ϕ = 270°. The mechanism of this proposal is owing to the hybrid polaritons supported by the polar thin film and nonreciprocal radiation of WSM, which is validated by examining the amplitude distribution of the magnetic field. The nonreciprocal emitter described herein allows simultaneous control of spectral distribution and polarization of radiation, which will facilitate the active design and application of mid-infrared (MIR) thermal emitters.

[Rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by diagnostic bronchoscopy].

OBJECTIVE: To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. METHODS: The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. RESULTS: The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×109/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO2/FiO2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO2/FiO2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. CONCLUSIONS: The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Bi-directional and multivariate mendelian randomization analysis of the relationship between circulating 25-hydroxyvitamin D concentration and obstructive sleep apnea.

BACKGROUND: 25-hydroxyvitamin D [25(OH)D] deficiency in patients with Obstructive Sleep Apnea (OSA) has long been noted, but identifying the exact causal relationship remains hard. Investigation of the causality between 25(OH)D deficiency and OSA would help facilitate disease prevention. METHODS: We conducted a two-sample bi-directional Mendelian randomization (MR) study. For forward analysis, 237 newly identified genetic variants are used as proxies for 25(OH)D to estimate the unconfounded effect on OSA among 16,761 OSA cases and 201,194 controls of European ancestry. Reverse analysis was performed to detect the causal impact of OSA on 25(OH)D levels. The inverse variance weighted (IVW) method was used as the primary analysis. Sensitivity analysis was performed to evaluate the robustness of our results. Multivariate MR analysis was conducted to evaluate the direct link between 25(OH)D and OSA after accounting for body mass index (BMI). RESULTS: IVW indicated that OSA causally associated with a lower level of 25(OH)D ((ß = -0.03, 95% CI = -0.06 ~ -0.007, P = 0.01). No evidence of the causal link from 25(OH)D to OSA was detected (OR = 0.99, 95% CI = 0.88 ~ 1.12, P = 0.85). Sensitivity analysis suggested the MR estimates were not biased. Multivariate MR analysis indicated the effect of OSA on 25(OH)D vanished upon accounting for BMI (ß = -0.011, 95% CI = -0.028 ~ 0.007, P = 0.23). CONCLUSION: This MR study provided evidence that OSA was causally associated with a lower level of 25(OH)D, which might be driven by BMI. Obesity management should be enhanced in patients with OSA to prevent 25(OH)D deficiency.

[Factors influencing the choice of endotracheal intubation and mechanical ventilation in patients with acute respiratory distress syndrome caused by viral pneumonia].

OBJECTIVE: To investigate the influencing factors of endotracheal intubation and mechanical ventilation (ETI-MV) in patients with acute respiratory distress syndrome (ARDS) caused by viral pneumonia, and to provide evidence for individualized use of ETI-MV. METHODS: Patients with ARDS due to viral pneumonia admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed from November 2017 to March 2022. The gender, age, concomitant diseases, clinical symptoms and signs, complications, lab results, ARDS severity, infectious virus type, acute physiology and chronic health evaluation II (APACHE II), respiratory support methods and prognosis-related variables were collected. Univariate analysis was performed on each factor, and the variables with statistical significance in the univariate analysis were subjected multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each index for the implementation of ETI-MV. RESULTS: A total of 117 patients were enrolled in the study, including 61 patients in the ETI-MV group, and 3 patients (4.9%), 39 patients (63.9%) and 19 patients (31.1%) with mild, moderate and severe ARDS, respectively. There were 56 patients in non-ETI-MV group, and the mild, moderate and severe ARDS cases were 16 cases (28.6%), 38 cases (67.8%) and 2 cases (3.6%), respectively. There was significant difference between the two groups (P < 0.05). Univariate analysis showed that during 24 hours admitted to RICU, the levels of interleukin-6 [IL-6 (ng/L): 104.0±90.0 vs. 62.4±76.0], oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 123.9±30.9 vs. 173.6±28.5], the proportion of cases with pulmonary infiltrating opacity distribution range ≥ 3/4 lung fields [85.3% (52/61) vs. 21.5% (12/56)], APACHE II score ≥ 16.5 [67.2% (41/61) vs. 42.9% (24/56)], the rate of nosocomial invasive aspergillus infection [14.8% (9/61) vs. 3.6% (2/56)], the percentage of nosocomial bacterial infection [16.4% (10/61) vs. 3.6% (2/56)], and the lowest CD4+ T lymphocyte count in the course of the disease [cells/mm3: 192.2±35.8 vs. 215.0±58.3] had significant differences between ETI-MV and non-ETI-MV group (all P < 0.05). Multivariate Logistic regression analysis showed that during 24 hours admitted to RICU the distribution range of pulmonary infiltrating opacity ≥ 3/4 the lung fields [odds ratio (OR) = 12.527, 95% confidence interval (95%CI) = 3.279-47.859, P < 0.001], APACHE II score ≥ 16.5 (OR = 30.604, 95%CI = 4.318-216.932, P = 0.001), PaO2/FiO2 (OR = 0.948, 95%CI = 0.925-0.972, P < 0.001), CD4+ T lymphocytes cell count (OR = 0.975, 95%CI = 0.955-0.995, P = 0.015), and nosocomial bacterial infection (OR = 38.338, 95%CI = 1.638-897.158, P = 0.023) were independent risk factors for ETI-MV. The area under the ROC curve (AUC) of ROC showed that PaO2/FiO2 had the greatest predictive value for ETI-MV, with AUC of 0.903, sensitivity of 91.1% and specificity of 95.1% in case of cutoff value of 151 mmHg. The AUC of pulmonary infiltrating opacity distribution range was 0.809, the sensitivity of 85.2%, specificity of 78.6% when the cutoff value was ≥ 3/4 lung field. APACHE II scores had the lowest predictive value for selecting ETI-MV, with AUC of 0.704, sensitivity of 83.6% and specificity of 57.1% under the cutoff value was 16.5. CONCLUSIONS: For patients with ARDS caused by viral pneumonia, PaO2/FiO2 is still the classic reference for selecting ETI-MV, however, the distribution range of pulmonary infiltrating opacity and the systemic severity of the disease during 24 hours admitted to the RICU may provide supplemental helpful information to determine whether the patients choose ETI-MV, especially for moderate ARDS.

[Comparative study on pros and cons of sequential high-flow nasal cannula and non-invasive positive pressure ventilation immediately following early extubated patients with severe respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme. METHODS: Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH2O (1 cmH2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH2O and the ratio of inspiratory to expiratory time 1.5-2.5:1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. RESULTS: Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). CONCLUSIONS: For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

[Expression of serous fibroblast growth factor 7 and related inflammatory factors in patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of fibroblast growth factor 7 (FGF7) and related inflammatory factors in the serum of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: A case control study was conducted. The patients with AECOPD admitted to the First Affiliated Hospital of Xinjiang Medical University from November 2016 to January 2020 were enrolled. The patients were divided into mild group [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC) < 0.70, FEV1 percentage in predicted value (FEV1%) ≥ 80%], moderate group (FEV1/FVC < 0.70, 50% ≤ FEV1% < 80%), and severe group (FEV1/FVC < 0.70, 30% ≤ FEV1% < 50%) based on their lung function test results, with 20 patients in each group, and 20 patients with normal pulmonary function who underwent elective non-thoracic surgery such as gastrointestinal surgery and orthopedics surgery in the same period were selected as controls. The demographic data, FEV1/FVC, FEV1%, FVC, maximum mid-expiratory flow percentage in predicted value (MMEF%), 6-minute walking test (6MWT), and St George Respiratory Questionnaire (SGRQ) score were recorded respectively. Serum levels of FGF7, interleukins (IL-6, IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Pearson correlation was used to analyze the correlation between TNF-α and lung function. RESULTS: Compared with the normal pulmonary function group, the levels of FEV1/FVC, FEV1%, MMEF% and 6MWT in the mild, moderate and severe groups were significantly decreased, and the SGRQ scores were increased, the indicators continued to deteriorate with the aggravation of the disease, the statistical differences were found between severe group and normal pulmonary function group [FEV1/FVC: 0.39±0.09 vs. 0.81±0.04, FEV1%: (38.80±6.28)% vs. (109.58±13.80)%, MMEF%: (0.34±0.14)% vs. (2.69±0.99)%, 6MWT (m): 279.00±41.61 vs. 402.85±53.97, SGRQ scores: 34.95±6.71 vs. 2.60±2.06, all P < 0.05]. Compared with the normal pulmonary function group, the levels of FGF7 in the mild, moderate and severe groups were significantly lowered (ng/L: 6.31±2.65, 6.10±1.39, 6.64±1.77 vs. 8.29±3.51, all P < 0.05), but no significant difference was found among the mild, moderate and severe groups (all P > 0.05). Compared with the normal pulmonary function group, IL-6 and TNF-α levels were significantly increased in the mild, moderate and severe groups, and TNF-α increased with the aggravation of the disease, the statistical difference was found between severe group and normal pulmonary function group (ng/L: 7.42±2.28 vs. 3.83±0.92, P < 0.05). There was no significant difference in IL-1ß level between the normal pulmonary function group and the mild, moderate, severe groups. Correlation analysis showed that TNF-α was negatively correlated with FEV1/FVC and FEV1% (r values were -0.350 and -0.527, respectively, both P < 0.01). CONCLUSIONS: In AECOPD patients, serum FGF7 was decreased, while IL-6 and TNF-α were increased; however, with the aggravation of the disease, there was no significant change in the level of FGF7 in the peripheral blood, but the TNF-α level might be increased, accompanied by severe damage of small airway function.

Silencing miR-125b-5p attenuates inflammatory response and apoptosis inhibition in mycobacterium tuberculosis-infected human macrophages by targeting DNA damage-regulated autophagy modulator 2 (DRAM2).

Tuberculosis is one of the most important infectious diseases worldwide and macrophage apoptosis is the major host defense mechanism against TB. We attempted to characterize the role of miRNA (miR)-125b-5p on mycobacterium tuberculosis (Mtb) infection and macrophages behaviors in vitro. According to fluorescence-activated cell separation (FACS), primary monocytes (CD14+) in TB patients were accumulated, and apoptotic monocytes were decreased. Peripheral blood mononuclear cells (PBMCs)-derived macrophages (MDMs) and monocytic cells THP-1-derived macrophage-like cells (TDMs) in vitro were used to be infected with H37Rv. After infection, colony-forming units assay revealed the increase of bacterial activity, FACS demonstrated the decrease of apoptosis rate of MDMs and TDMs, as well as promoted levels of IL-6, TNF-α, Bax, and Bim and suppressed levels of IL-10 and Bcl-2, examined by enzyme-linked immunosorbent assay (ELISA) and western blot assay. Expression of miR-125b-5p and DNA damage-regulated autophagy modulator 2 (DRAM2) was examined, and real-time PCR and western blot assay showed that miR-125b-5p was upregulated, whereas DRAM2 was downregulated in primary monocytes and H37Rv-infected macrophages (MDMs and TDMs). Moreover, blocking miR-125b-5p could attenuated H37Rv-induced bacterial activity and inflammatory response of MDMs and TDMs, accompanied with apoptosis inhibition. Whereas these effects of miR-125b-5p knockdown were abolished by downregulating DRAM2. In mechanism, DRAM2 was a downstream target of miR-125b-5p, as evidenced by dual-luciferase reporter assay. Collectively, silencing miR-125b-5p could protect human macrophages against Mtb infection through promoting apoptosis and inhibiting inflammatory response via targeting DRAM2, suggesting a novel target for Mtb eliminating. Abbreviations: TB: tuberculosis; PBMCs: peripheral blood mononuclear cells; Mtb: mycobacterium tuberculosis; AFB: acid fast bacilli; FITC: fluorescein isothiocyanate; MDMs: monocytes-derived macrophages; TDMs: THP-1-derived macrophage-like cells; ERFP: Mtb-enhanced red fluorescent protein; CFU: colony-forming units; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell separation; PI: propidium iodide; DRAM2: DNA damage-regulated autophagy modulator 2; Real-time PCR: real-time polymerase chain reaction; in-miR-125b-5p: miR-125b-5p inhibitor; si-DRAM2: siRNA against DRAM2.

[Timing of sequential noninvasive mechanical ventilation following early extubation in aged patients with severe community-acquired pneumonia].

OBJECTIVE: To explore the timing of sequential noninvasive positive pressure ventilation (NIPPV) following endotracheal intubation mechanical ventilation (ETI-MV) in aged patients with severe community-acquired pneumonia (SCAP). METHODS: A prospective cohort study was conducted. The SCAP patients aged ≥ 75 years old admitted to respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to August 2019 were enrolled. SCAP was diagnosed according to the criteria of Guidelines for the diagnosis and treatment of community-acquired pneumonia in adults in China (2016) published by Chinese Thoracic Society. ETI-MV was initially performed as respiratory support after RICU admission. Sequential NIPPV was performed immediately following extubation when the patients exhibited pulmonary infection abated (PIA) window. The gender, age, underlying diseases, and body temperature, heart rate (HR), respiratory rate (RR), oxygenation index (PaO2/FiO2) after RICU admission, as well as acute physiology and chronic health evaluation II (APACHE II) score, improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and pneumonia severity index (PSI) score within 24 hours after RICU admission were recorded. The duration and times of ETI, the incidences of ventilator associated pneumonia (VAP) and aspiration, the duration of mechanical ventilation (MV), the length of RICU and hospital stay and RICU prognosis were also recorded. The patients were divided into the ETI ≤ 7 days group and the ETI > 7 days group according to the duration of ETI, and the clinical data were compared between the two groups. Multivariate Logistic regression analysis was used to screen the risk factors of aged patients with SCAP whose ETI was more than 7 days, and receiver operator characteristic (ROC) curve was drawn to evaluate the predictive value of risk factors. RESULTS: Fifty aged patients with SCAP were enrolled, with 24 patients in the ETI ≤ 7 days group and 26 in the ETI > 7 days group. Univariate analysis showed that compared with the patients with ETI ≤ 7 days, the incidences of concurrent cerebrovascular diseases [46.2% (12/26) vs. 16.7% (4/24)], VAP [61.5% (16/26) vs. 16.7% (4/24)] and aspiration [69.2% (18/26) vs. 25.0% (6/24)] were significantly increased in patients with ETI > 7 days (all P < 0.05). Multivariate Logistic regression analysis indicated that VAP and aspiration were independent risk factors of ETI > 7 days in the aged SCAP patients [VAP: odds ratio (OR) = 4.852, 95% confidence interval (95%CI) was 1.076-21.877, P = 0.040; aspiration: OR = 5.903, 95%CI was 1.474-23.635, P = 0.012]. ROC curve analysis showed that the area under ROC curve (AUC) of VAP for predicting ETI > 7 days in aged patients with SCAP was 0.724, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index were 61.54%, 83.33%, 80.00%, 66.67%, 3.69, 0.46 and 0.45, respectively. Similarly, the AUC of aspiration was 0.721, the sensitivity, specificity, PPV, NPV, PLR, NLR and Youden index were 69.23%, 75.00%, 75.00%, 69.23%, 2.77, 0.41 and 0.44, respectively. Analysis of prognostic indicators showed that compared with patients with ETI ≤ 7 days, the reintubation rate and RICU mortality were significantly increased in patients with ETI > 7 days [53.8% (14/26) vs. 4.2% (1/24), 38.5% (10/26) vs. 12.5% (3/24), both P < 0.05]. Moreover, the patients with ETI > 7 days had significantly prolonged total duration of MV, the length of RICU stay and total hospital stay as compared with the patients with ETI ≤ 7 days [total duration of MV (days): 23.8±11.8 vs. 11.3±3.1, length of RICU stay (days): 30.6±14.1 vs. 16.0±5.1, total length of hospital stay (days): 33.0±14.9 vs. 20.2±6.1, all P < 0.01]. CONCLUSIONS: Sequential NIPPV performed immediately following extubation within 7 days in the aged SCAP patients might reduce the mortality and shorten the duration of MV. The prolonged ETI duration because of the VAP or aspiration would lead to a reduced function of sequential NIPPV and an increased mortality of the aged patients with SCAP.

Circ_0038467 regulates lipopolysaccharide-induced inflammatory injury in human bronchial epithelial cells through sponging miR-338-3p.

BACKGROUND: Pneumonia is a common acute lower respiratory infection in children and elders. Circular RNAs (circRNAs) have recently been uncovered to play important roles in pneumonia. However, the function and mechanism of circ_0038467 in pneumonia remain elusive. METHODS: Cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The levels of interleukin 6 (IL-6), IL-8 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to assess the expression of related proteins. Circ_0038467 was characterized by Ribonuclease R (RNase) digestion and subcellular localization assays. The levels of circ_0038467 and miR-338-3p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The direct interaction between circ_0038467 and miR-338-3p was validated by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our data indicated that lipopolysaccharide (LPS) induced an inflammatory injury in 16HBE cells by repressing cell viability and enhancing cell apoptosis and proinflammatory cytokines production. Circ_0038467 was upregulated and miR-338-3p was downregulated in LPS-treated 16HBE cells. Circ_0038467 knockdown or miR-338-3p overexpression attenuated LPS-induced 16HBE cell inflammatory injury. Moreover, circ_0038467 acted as a sponge of miR-338-3p in 16HBE cells. MiR-338-3p mediated the alleviated effect of circ_0038467 knockdown on LPS-induced 16HBE cell inflammatory injury. Additionally, the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was involved in the circ_0038467/miR-338-3p axis-mediated regulation in LPS-induced 16HBE cell inflammatory injury. CONCLUSIONS: The current work had led to the identification of circ_0038467 knockdown that alleviated LPS-induced inflammatory injury in 16HBE cells at least partly through sponging miR-338-3p and regulating JAK/STAT3 pathway, highlighting novel molecular targets for the treatment of pneumonia.

[Predictive factors for failure of non-invasive positive pressure ventilation in immunosuppressed patients with acute respiratory failure].

OBJECTIVE: To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). METHODS: The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. RESULTS: The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO2) was significantly decreased, the ratio of oxygenation index (PaO2/FiO2) < 100 mmHg (1 mmHg = 0.133 kPa), acute physiology and chronic health evaluation II (APACHE II) score ≥ 20, and the number of cases requiring catecholamine were significantly increased, the mortality was significantly increased. Multivariate Logistic regression analysis showed that the APACHE II score ≥ 20 [odds ratio (OR) = 15.274, 95% confidence internal (95%CI) = 2.175-107.252, χ2 = 7.516, P = 0.006], PaO2/FiO2 < 100 mmHg (OR = 0.075, 95%CI = 0.014-0.408, χ2 = 8.968, P = 0.003), and need for catecholamine (OR = 35.736, 95%CI = 6.974-183.124, χ2 = 18.400, P < 0.001) were independent risk factors for failure of NIPPV. ROC curve analysis showed that the APACHE II score ≥ 20 and PaO2/FiO2 < 100 mmHg could predict failure of NIPPV, the area under ROC curve (AUC) of the APACHE II score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO2/FiO2 < 100 mmHg was 0.757, the sensitivity was 80.65%, the specificity was 66.07%, the PPV was 68.18%, the NPV was 78.85%, the PLR was 2.38, the NLR was 0.29, and Youden index was 0.47. CONCLUSIONS: 50.8% of immunocompromised and ARF patients treated with NIPPV did not require ETI, which is independent of the etiology of ARF. APACHE II score ≥ 20, PaO2/FiO2 < 100 mmHg, and the need for catecholamine are predictive factors for failure of NIPPV in immunocompromised patients.

Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population.

AIM: Adiponectin has been implicated in the development of chronic obstructive pulmonary disease (COPD). The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. METHODS: Ten single-nucleotide polymorphisms (SNP) in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models. RESULTS: Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, P=0.022). The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC (P<0.05). Haplotypes GC in block 1 (rs4783244-rs12922394) as well as GTAC and ATGT in block 3 (rs4783266-rs11640522-rs11646849-rs11860282) significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 (rs11646011- rs11640875) and ATGC in block 3 were protective against COPD. CONCLUSION: CDH13 genetic variants determine Chinese individuals' susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD.

[An investigation of the efficacy of invasive-noninvasive sequential mechanical ventilation in senile patients with severe community-acquired pneumonia].

OBJECTIVE: To investigate the efficacy of invasive-noninvasive sequential mechanical ventilation (MV) in senile patients with severe community-acquired pneumonia (CAP). METHODS: A prospective study was conducted. The patients with severe CAP aged ≥75 years admitted to Department of Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from November 2012 to July 2014, with refusal to have tracheostomy, were enrolled. All patients meeting the diagnostic criteria of CAP and severe CAP were first admitted into the Department of Emergency, and they were found to need MV without absolute contraindication for noninvasive ventilation (NIV) in RICU. The patients were mechanically ventilated via endotracheal intubation (ETI), and they were randomly divided into invasive-noninvasive sequential MV group (sequential MV group) and conventional MV group. NIV was initiated immediately when patients matched the conditions for early extubation in the sequential MV group. Oxygen therapy (5 L/min) via a Venturi mask was provided when the indications of conventional extubation were met. The baseline data and clinical characteristics were recorded, the risk factors of death were analyzed by logistic regression analysis, and 60-day survival rate was analyzed by Kaplan-Meier curve. RESULTS: Ninety-one senile patients with severe CAP were enrolled, among them 28 patients died within 60 days, with a mortality rate of 30.77%. No significant difference in 60-day mortality was found between sequential MV group (n=44) and conventional MV group [n=47, 25.0% (11/44) vs. 36.2% (17/47), χ2=1.331, P=0.249]. In the sequential MV group, the incidence of ventilator-associated pneumonia (VAP) was significantly decreased [27.3% (12/44) vs. 55.3% (26/47), χ2=7.350, P=0.007], and the rate of ETI≥2 times was increased [59.1% (26/44) vs. 29.8% (14/47), χ2=5.095, P=0.024] as compared with conventional MV group. Compared with survival group, the patients in non-survival group showed a higher incidence of cerebrovascular disease (60.7% vs. 25.4%, P=0.002), higher acute physiology and chronic health evaluation II (APACHEII) score (26.46±2.59 vs. 24.41±2.47, P=0.001), British Thoracic Society confusion, uremia, respiratory rate, blood pressure, ≥75 years (CURB-75 score, 4.00±0.47 vs. 3.68±0.53, P=0.013), a longer total duration of MV (days: 21.18±10.02 vs. 14.56±7.62, P=0.002), and a higher ratio of ETI≥2 times (53.6% vs. 33.3%, P<0.001). It was revealed by multivariate logistic regression analysis that ETI≥2 times and comorbidity of cerebrovascular infarction were independent predictors of a worse outcome in the senile patients [odds ratio (OR)=9.677, 95% confidence interval (95%CI)=3.075-30.457, P<0.001; OR=5.386, 95%CI=1.781-6.284, P=0.003]. It was showed by Kaplan-Meir survival analysis that ETI times and concurrent cerebrovascular infarction imparted significant effects on the 60-day survival rate (χ2=40.805, P=0.000; χ2=4.425, P=0.035). CONCLUSIONS: Invasive-noninvasive sequential MV may not improve the outcome of senile patients with severe CAP, and ETI≥2 times and concurrent cerebrovascular disorders drastically lowered the survival rate.

[Study of timing of invasive and noninvasive sequential ventilation in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the timing and value of noninvasive ventilation (NIV) as a weaning tool immediately after early extubation in patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective randomized controlled trial was conducted. The ARDS patients with surgical diseases admitted to Department of Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were enrolled. The patients were randomly divided into sequential group and control group. All patients underwent endotracheal intubation and were mechanically ventilated. Every 12 hours during the first 3 days, the lung recruitment maneuver was performed during pressure control ventilation (PCV). After lung recruitment, all patients were ventilated with synchronized intermittent mandatory ventilation (SIMV) + pressure support ventilation (PSV) + positive end-expiratory pressure (PEEP) or assistant/control ventilation (A/C). The objects in sequential group who met the following criteria including those with oxygen index (PaO2/FiO2) reaching 200-250 mmHg (1 mmHg=0.133 kPa) under PEEP of 8 cmH2O (1 cmH2O=0.098 kPa), and pressure support of 12 cmH2O, and most acute infiltrating lesions having resolved on chest imaging, received noninvasive ventilation (NIV) immediately after extubation, and patients in control group continued to have invasive mechanical ventilation via intubation or tracheostomy with an endotracheal tube. The baseline data in both groups and the number of re-intubation in the sequential group were recorded. The duration of invasive mechanical ventilation and total duration of mechanical ventilation, ICU length of stay, the incidence of ventilator-associated pneumonia (VAP), and mortality rate were compared between the two groups. RESULTS: 53 consecutive adult patients were enrolled, including 26 in sequential group and 27 cases in control group. The period of endotracheal intubation was 7.0 (6.8, 9.5) days, and 7.7% (2/26) patients underwent re-intubation in sequential group. There were significant difference in respiratory and circulatory indicators before extubation spontaneous breathing trial (SBT) ≤10 minutes in sequential group, indicating that the patients were still in the early stage of extubation sequential NIV. There was no significant difference in indices reflecting respiratory function and circulation between the two groups, except that respiratory rate at 1 hour was slightly increased in sequential group as compared with that of control group, indicating that sequential NIV could maintain invasive ventilation function. There was significant difference in duration of invasive mechanical ventilation [7.0 (6.8, 9.5) days vs. 21.0 (17.0, 25.0) days, Z=-6.048, P=0.000], duration of total mechanical ventilation (18.0±4.1 days vs. 22.0±7.3 days, t=-2.805, P=0.008), and length of ICU stay (21.0±4.1 days vs. 28.0±8.1 days, t=-4.012, P=0.000) between sequential group and control group, but there was no significant differences in the incidence of VAP [15.4% (4/26) vs. 29.6 (8/27), χ(2)=1.535, P=0.215] and mortality rate [7.7% (2/26) vs. 18.5% (5/27), P=0.420]. CONCLUSIONS: When PaO2/FiO2 reached 200-250 mmHg under the condition of low ventilation, sequential NIV facilitates the early discontinuation of mechanical ventilation in ARDS patients with surgical diseases, with shortening of duration of invasive mechanical ventilation, total mechanical ventilation, and the length of ICU stay.

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese.

OBJECTIVES: Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. METHODS: Seven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case-control study (680 COPD patients and 687 controls). Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis. RESULTS: Statistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003-0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P=0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r(2) ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P=0.2356, 0.1273, 0.6266 and 0.3006 respectively). CONCLUSIONS: The current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.